{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:11:38Z","timestamp":1788952298554,"version":"build-2803163510"},"reference-count":319,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Non-small cell lung cancer is one of the leading causes of cancer-related mortality. The effectiveness of treatment is limited by several factors, including significant tumoral heterogeneity, rapid development of drug resistance, high metastatic potential, and a complex tumor microenvironment. In recent years, natural products have emerged as valuable resources for the discovery of novel antitumor strategies against non-small cell lung cancer. These compounds possess diverse chemical properties, target multiple pathways, are abundant in nature, and exhibit relatively low toxicity. The utilization of existing medications with established pharmacokinetic profiles and safety records, combined with shorter development timelines, shows promise for advancing lung cancer treatment research. A growing body of evidence indicates that both naturally occurring compounds and commercially available drugs exert effects that extend beyond traditional cytotoxic mechanisms. These agents influence processes such as ferroptosis, oxidative stress, metabolic reprogramming, autophagy, apoptosis, epithelial\u2013mesenchymal transition (EMT), tumor immune microenvironments, and epigenetic networks, suggesting that their activities can be leveraged for a robust multi-target antitumor strategy. Accordingly, this review summarizes research advances on natural products and repurposed marketed drugs for non-small cell lung cancer; outlines their potential for combination with chemotherapy, targeted therapy, radiotherapy and immunotherapy; and discusses future directions for clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27177908","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:25:56Z","timestamp":1788542756000},"page":"7908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges"],"prefix":"10.3390","volume":"27","author":[{"given":"Yuli","family":"Xie","sequence":"first","affiliation":[{"name":"West China School of Pharmacy, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"West China School of Pharmacy, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Tang","sequence":"additional","affiliation":[{"name":"West China School of Pharmacy, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.2147\/IJN.S521444","article-title":"Advancements in nanocarrier delivery systems for photodynamic therapy in lung cancer","volume":"20","author":"Wang","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/ptr.70218","article-title":"Recent Advances in Natural Products for Cancer Immunotherapy","volume":"40","author":"Liu","year":"2026","journal-title":"Phytother. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1080\/1354750X.2022.2055147","article-title":"Prognostic value of pre-treatment advanced lung cancer inflammation index in non-small cell lung cancer: A meta-analysis","volume":"27","author":"Tang","year":"2022","journal-title":"Biomarkers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3892\/mco.2025.2837","article-title":"Treatment of advanced-stage non-small cell lung cancer: Current progress and a glimpse into the future (Review)","volume":"22","author":"Wang","year":"2025","journal-title":"Mol. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/s41417-024-00761-z","article-title":"Hippo pathway in non-small cell lung cancer: Mechanisms, potential targets, and biomarkers","volume":"31","author":"Liang","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.2174\/1389201025666230830125410","article-title":"Insights on quercetin therapeutic potential for neurodegenerative diseases and its nano-technological perspectives","volume":"25","author":"Goyal","year":"2024","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Xiang, Y., Liu, X., Wang, Y., Zheng, D., Meng, Q., Jiang, L., Yang, S., Zhang, S., Zhang, X., and Liu, Y. (2024). Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: Promising strategies to overcoming challenges. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1366260"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1080\/1061186X.2018.1450413","article-title":"Preparation and anti-cancer evaluation of promiximab-MMAE, an anti-CD56 antibody drug conjugate, in small cell lung cancer cell line xenograft models","volume":"26","author":"Yu","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"105766","DOI":"10.1016\/j.intimp.2019.105766","article-title":"Interleukin-9 promotes tumorigenesis through augmenting angiogenesis in non-small cell lung cancer","volume":"75","author":"He","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118340","DOI":"10.1016\/j.jep.2024.118340","article-title":"Disruption of NADPH homeostasis by total flavonoids from Adinandra nitida Merr. ex Li leaves triggers ROS-dependent p53 activation leading to apoptosis in non-small cell lung cancer cells","volume":"332","author":"Lan","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1007\/s11418-023-01772-0","article-title":"Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability","volume":"78","author":"Wang","year":"2024","journal-title":"J. Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1038\/s41401-020-00606-z","article-title":"Surface loading of nanoparticles on engineered or natural erythrocytes for prolonged circulation time: Strategies and applications","volume":"42","author":"Zhang","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Oh, M.S., Abascal, J., Rennels, A.K., Salehi-Rad, R., Dubinett, S.M., and Liu, B. (2025). Tumor Heterogeneity and the Immune Response in Non-Small Cell Lung Cancer: Emerging Insights and Implications for Immunotherapy. Cancers, 17.","DOI":"10.3390\/cancers17061027"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1200\/JCO.23.00580","article-title":"Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non\u2013Small-Cell Lung Cancer","volume":"42","author":"Ricciuti","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/1568009623666230414140609","article-title":"Identification of necroptosis-related subtypes and characterization of tumor microenvironment infiltration in non-small cell lung cancer","volume":"24","author":"Deng","year":"2024","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.2174\/0115748928283728240320063619","article-title":"Fat-soluble Vitamins and Lung Cancer: Where We Are?","volume":"20","author":"Lin","year":"2025","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1002\/ptr.7154","article-title":"Erianin inhibits human lung cancer cell growth via PI3K\/Akt\/mTOR pathway in vitro and in vivo","volume":"35","author":"Zhang","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lei, Y., Jiang, S., Kong, C., Pang, P., and Shan, H. (2025). Ferroptosis: Therapeutic Potential and Strategies in Non-Small Cell Lung Cancer. Biology, 14.","DOI":"10.3390\/biology14050545"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41420-025-02308-z","article-title":"Targeting ferroptosis: A promising approach for treating lung carcinoma","volume":"11","author":"Wu","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Xia, Y., Wang, F., Yang, D., and Liang, Z. (2024). Induction of ferroptosis by natural products in non-small cell lung cancer: A comprehensive systematic review. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1385565"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115535","DOI":"10.1016\/j.taap.2021.115535","article-title":"Nannocystin Ax, a natural elongation factor 1\u03b1 inhibitor from Nannocystis sp., suppresses epithelial-mesenchymal transition, adhesion and migration in lung cancer cells","volume":"420","author":"Sun","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3935","DOI":"10.1016\/j.apsb.2021.07.029","article-title":"DNA-PK inhibition by M3814 enhances chemosensitivity in non-small cell lung cancer","volume":"11","author":"Wang","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101145","DOI":"10.1016\/j.jpha.2024.101145","article-title":"Natural products for the treatment of age-related macular degeneration: New insights focusing on mitochondrial quality control and cGAS\/STING pathway","volume":"15","author":"Xie","year":"2025","journal-title":"J. Pharm. Anal."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.2147\/IJN.S466315","article-title":"Nanomedicines targeting tumor cells or tumor-associated macrophages for combinatorial cancer photodynamic therapy and immunotherapy: Strategies and influencing factors","volume":"19","author":"Wei","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155503","DOI":"10.1016\/j.phymed.2024.155503","article-title":"Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential","volume":"127","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_26","first-page":"39","article-title":"Comparison of the effects of natural, cultivated, and synthetic musk on preventing acute cerebral ischemia\/reperfusion injury in rats","volume":"46","author":"Liang","year":"2025","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"155600","DOI":"10.1016\/j.phymed.2024.155600","article-title":"Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism","volume":"129","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155608","DOI":"10.1016\/j.phymed.2024.155608","article-title":"Targeting CD8+ T cells with natural products for tumor therapy: Revealing insights into the mechanisms","volume":"129","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Campos-Parra, A.D., Leyva-Gomez, G., and Padilla-Benavides, T. (2025). Editorial: Repurposed drugs targeting cancer signaling pathways: Clinical insights to improve oncologic therapies, volume II. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1628842"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, Y., An, J., Zhou, J., Chang, L., Zhang, Q., and Peng, F. (2025). Hydroxysafflor yellow A: A natural pigment with potential anticancer therapeutic effect. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1495393"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, Q., Ruan, D., Shi, J., Du, D., and Bian, C. (2023). The multifaceted roles of natural products in mitochondrial dysfunction. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1093038"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Land, K.M., Huang, C., and Zhang, Y.-Y. (2023). Natural products as drug candidates for redox-related human disease. Pharmaceuticals, 16.","DOI":"10.3390\/ph16091294"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"154520","DOI":"10.1016\/j.phymed.2022.154520","article-title":"The International Natural Product Sciences Taskforce (INPST) and the power of Twitter networking exemplified through# INPST hashtag analysis","volume":"108","author":"Singla","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41420-025-02328-9","article-title":"Insights on the crosstalk among different cell death mechanisms","volume":"11","author":"Eskander","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"177414","DOI":"10.1016\/j.ejphar.2025.177414","article-title":"Crosstalk between autophagy and other forms of programmed cell death","volume":"995","author":"Wang","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/bcp.15336","article-title":"Analysis of adverse event of interstitial lung disease in men with prostate cancer receiving hormone therapy using the Food and Drug Administration Adverse Event Reporting System","volume":"89","author":"Wu","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, L., Wang, B., Ma, L., and Fu, P. (2022). Traditional Chinese herbs and natural products in hyperuricemia-induced chronic kidney disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.971032"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rahman, M.M., Wang, X., Islam, M.R., Akash, S., Supti, F.A., Mitu, M.I., Harun-Or-Rashid, M., Aktar, M.N., Khatun Kali, M.S., and Jahan, F.I. (2022). Multifunctional role of natural products for the treatment of Parkinson\u2019s disease: At a glance. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.976385"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103148","DOI":"10.1016\/j.tice.2025.103148","article-title":"Mechanisms of mitochondrial autophagy-mediated crosstalk between ferroptosis and cuproptosis in lung cancer","volume":"98","author":"Jiang","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3892\/ijmm.2026.5779","article-title":"The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review)","volume":"57","author":"Zhang","year":"2026","journal-title":"Int. J. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Singla, R.K., He, X., Chopra, H., Tsagkaris, C., Shen, L., Kamal, M.A., and Shen, B. (2021). Natural products for the prevention and control of the COVID-19 pandemic: Sustainable bioresources. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.758159"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Singla, R.K., Sharma, P., Dubey, A.K., Gundamaraju, R., Kumar, D., Kumar, S., Madaan, R., Shri, R., Tsagkaris, C., and Parisi, S. (2021). Natural product-based studies for the management of castration-resistant prostate cancer: Computational to clinical studies. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.732266"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1002\/ptr.8217","article-title":"Luteolin: A promising multifunctional natural flavonoid for human diseases","volume":"38","author":"Zhu","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Hou, W., Huang, L., Huang, H., Liu, S., Dai, W., Tang, J., Chen, X., Lu, X., Zheng, Q., and Zhou, Z. (2024). Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review. Molecules, 29.","DOI":"10.3390\/molecules29020540"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2018.04.005","article-title":"Theranostic size-reducible and no donor conjugated gold nanocluster fabricated hyaluronic acid nanoparticle with optimal size for combinational treatment of breast cancer and lung metastasis","volume":"278","author":"Liu","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"153782","DOI":"10.1016\/j.phymed.2021.153782","article-title":"Natural products: Potential targets of TME related long non-coding RNAs in lung cancer","volume":"93","author":"Malla","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1039\/C9NP00003H","article-title":"En route to terpene natural products utilizing supramolecular cyclase mimetics","volume":"36","author":"Zhang","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/1440-1681.13287","article-title":"The combination of artesunate and carboplatin exerts a synergistic anti-tumour effect on non-small cell lung cancer","volume":"47","author":"Wang","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4126","DOI":"10.1007\/s13346-025-01923-8","article-title":"Traversing the Valley of Death for nanotechnology-based natural products: Strategies and insights from pharmaceutical stakeholders","volume":"15","author":"Loh","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107","DOI":"10.36468\/pharmaceutical-sciences.spl.339","article-title":"The Effect of Dezocine Combined with Oxycodone in the Treatment of Advanced Lung Cancer with Bone Metastasis and Severe Cancer Pain on the Numerical Rating Scale Score of Patients","volume":"83","author":"Yan","year":"2021","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3892\/mco.2024.2779","article-title":"Targeting signaling pathways with andrographolide in cancer therapy (Review)","volume":"21","author":"Shaharudin","year":"2024","journal-title":"Mol. Clin. Oncol."},{"key":"ref_52","first-page":"13","article-title":"Research advances in natural sesquiterpene lactones: Overcoming cancer drug resistance through modulation of key signaling pathways","volume":"8","author":"Teng","year":"2025","journal-title":"Cancer Drug Resist."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Naponelli, V., Rocchetti, M.T., and Mangieri, D. (2024). Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105569"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zeng, W., Zheng, S., Mao, Y., Wang, S., Zhong, Y., Cao, W., Su, T., Gong, M., Cheng, J., and Zhang, Y. (2021). Elevated N-Glycosylation Contributes to the Cisplatin Resistance of Non-Small Cell Lung Cancer Cells Revealed by Membrane Proteomic and Glycoproteomic Analysis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.805499"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yang, D., Peng, D., Li, H., Jia, D., Zhou, Y., Hu, B., Chen, W., and Meng, Y. (2025). The type I ribosome-inactivating protein \u03b1-MMC induced significant apoptosis of lung cancer A549 and 95-D cells by activating the caspase cascade through TNF signaling pathway. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1529151"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"116037","DOI":"10.1016\/j.taap.2022.116037","article-title":"Mogrol suppresses lung cancer cell growth by activating AMPK-dependent autophagic death and inducing p53-dependent cell cycle arrest and apoptosis","volume":"444","author":"Li","year":"2022","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yin, R., Zhang, Y., Su, L., Chen, D., Lou, S., Luo, X., Wang, L., Tang, R., Zhang, L., and Tian, X. (2023). The mechanism of trans-\u03b4-viniferin inhibiting the proliferation of lung cancer cells A549 by targeting the mitochondria. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1190127"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"113684","DOI":"10.1016\/j.bcp.2019.113684","article-title":"Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells","volume":"171","author":"Liu","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ye, Q., Zhou, L., Jin, P., Li, L., Zheng, S., Huang, Z., Liu, J., Qin, S., Liu, H., and Zou, B. (2021). Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.621181"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"116406","DOI":"10.1016\/j.biopha.2024.116406","article-title":"Bioactivity and mechanism of action of sanguinarine and its derivatives in the past 10 years","volume":"173","author":"Huang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109336","DOI":"10.1016\/j.biopha.2019.109336","article-title":"Negative regulators of Wnt signaling in non-small cell lung cancer: Theoretical basis and therapeutic potency","volume":"118","author":"Song","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_62","first-page":"1128","article-title":"Knockdown of HJURP inhibits non-small cell lung cancer cell proliferation, migration, and invasion by repressing Wnt\/\u03b2-catenin signaling","volume":"23","author":"Wei","year":"2019","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nigam, M., Punia, B., Dimri, D.B., Mishra, A.P., Radu, A.-F., and Bungau, G. (2025). Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics. Cells, 14.","DOI":"10.3390\/cells14151207"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s10787-024-01596-8","article-title":"The multifaceted anticancer potential of luteolin: Involvement of NF-\u03baB, AMPK\/mTOR, PI3K\/Akt, MAPK, and Wnt\/\u03b2-catenin pathways","volume":"33","author":"Singh","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"156890","DOI":"10.1016\/j.phymed.2025.156890","article-title":"Sophora compounds against non-small cell lung cancer: Research status and mechanisms","volume":"143","author":"Ye","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Virchea, L.-I., Frum, A., Georgescu, C., Pecsenye, B., M\u00e1th\u00e9, E., Mironescu, M., Cr\u0103ciuna\u0219, M.-T., Totan, M., T\u0103n\u0103sescu, C., and Gligor, F.-G. (2025). An Overview of the Bioactivity of Spontaneous Medicinal Plants Suitable for the Improvement of Lung Cancer Therapies. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17030336"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Dong, J., Li, B., Lin, D., Zhou, Q., and Huang, D. (2019). Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00230"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1097\/CAD.0000000000001133","article-title":"Comorbidities and mortality risk among extensive-stage small-cell lung cancer patients in mainland China: Impacts of hypertension, type 2 diabetes mellitus, and chronic hepatitis B virus infection","volume":"33","author":"Xiu","year":"2021","journal-title":"Anti-Cancer Drugs"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/CM9.0000000000002693","article-title":"Molecular classification of small cell lung cancer subtypes: Characteristics, prognostic factors, and clinical translation","volume":"137","author":"Guo","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Boldig, C., Boldig, K., Mokhtari, S., and Etame, A.B. (2024). A Review of the Molecular Determinants of Therapeutic Response in Non-Small Cell Lung Cancer Brain Metastases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25136961"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13045-025-01690-6","article-title":"Current and future therapies for small cell lung carcinoma","volume":"18","author":"Zhai","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1111\/cas.16192","article-title":"Histologic transformation of non-small-cell lung cancer in response to tyrosine kinase inhibitors: Current knowledge of genetic changes and molecular mechanisms","volume":"115","author":"Takemura","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wu, Y., Wang, Z., Yang, Y., Han, C., Wang, L., Kang, K., and Zhao, A. (2023). Exploration of potential novel drug targets and biomarkers for small cell lung cancer by plasma proteome screening. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1266782"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Luan, Y., Xian, D., Zhao, C., Qing, X., He, H., Zheng, K., Song, W., Jiang, T., Wang, W., and Duan, C. (2024). Therapeutic targets for lung cancer: Genome-wide Mendelian randomization and colocalization analyses. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1441233"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Joshi, A., Bhaskar, N., and Pearson, J.D. (2025). Neuroendocrine Transformation as a Mechanism of Resistance to Targeted Lung Cancer Therapies: Emerging Mechanisms and Their Therapeutic Implications. Cancers, 17.","DOI":"10.3390\/cancers17020260"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"150395","DOI":"10.1016\/j.bbrc.2024.150395","article-title":"Expression of the non-coding RNA nc886 facilitates the development of tyrosine kinase inhibitor resistance in EGFR-mutated non-small-cell lung cancer cells","volume":"731","author":"Bui","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"112283","DOI":"10.1016\/j.jep.2019.112283","article-title":"Mechanistic and therapeutic study of novel anti-tumor function of natural compound imperialine for treating non-small cell lung cancer","volume":"247","author":"Lin","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1091\/mbc.E24-08-0370","article-title":"DNA damage\u2013induced EMT controlled by the PARP-dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells","volume":"35","author":"Rajabi","year":"2024","journal-title":"Mol. Biol. Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12032-024-02586-0","article-title":"GRP78 as a potential therapeutic target in cancer treatment: An updated review of its role in chemoradiotherapy resistance of cancer cells","volume":"42","author":"Lin","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4929","DOI":"10.1038\/s41467-025-60223-4","article-title":"RNF20 links the DNA damage response and metabolic rewiring in lung cancer through HIF1\u03b1","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e2412854122","DOI":"10.1073\/pnas.2412854122","article-title":"The oncoprotein SET promotes serine-derived one-carbon metabolism by regulating SHMT2 enzymatic activity","volume":"122","author":"Jiao","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1515\/mr-2024-0091","article-title":"Histone lactylation as a driver of metabolic reprogramming and immune evasion","volume":"5","author":"Cai","year":"2025","journal-title":"Med. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/s41586-024-08439-0","article-title":"Immune evasion through mitochondrial transfer in the tumour microenvironment","volume":"638","author":"Ikeda","year":"2025","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Gong, X., Zhou, Y., and Deng, Y. (2025). Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32070367"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/1354750X.2020.1731763","article-title":"Prognostic value of pre-treatment red blood cell distribution width in lung cancer: A meta-analysis","volume":"25","author":"Wang","year":"2020","journal-title":"Biomarkers"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jconrel.2022.06.063","article-title":"Peritoneal M2 macrophage-derived extracellular vesicles as natural multitarget nanotherapeutics to attenuate cytokine storms after severe infections","volume":"349","author":"Wang","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"105615","DOI":"10.1016\/j.phrs.2021.105615","article-title":"Naturally occurring coumestans from plants, their biological activities and therapeutic effects on human diseases","volume":"169","author":"Tu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Ma, L., and Luo, J. (2021). Chondroitin sulfate-modified liposomes for targeted co-delivery of doxorubicin and retinoic acid to suppress breast cancer lung metastasis. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13030406"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1208\/s12249-021-02084-w","article-title":"Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF: A Novel Anticancer Drug for the Treatment of Non-small Cell Lung Cancer: Physicochemical Characterization and Biopharmaceutical Evaluation of ZWF","volume":"22","author":"Zhao","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/1061186X.2020.1797050","article-title":"Opportunities and obstacles of targeted therapy and immunotherapy in small cell lung cancer","volume":"29","author":"Yu","year":"2021","journal-title":"J. Drug Target."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"110795","DOI":"10.1016\/j.cbi.2023.110795","article-title":"Phytosphingosine inhibits the growth of lung adenocarcinoma cells by inducing G2\/M-phase arrest, apoptosis, and mitochondria-dependent pathway cell death in vitro and in vivo","volume":"387","author":"Cai","year":"2024","journal-title":"Chem. Biol. Interact."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Rajabi, S., Maresca, M., Yumashev, A.V., Choopani, R., and Hajimehdipoor, H. (2021). The Most Competent Plant-Derived Natural Products for Targeting Apoptosis in Cancer Therapy. Biomolecules, 11.","DOI":"10.3390\/biom11040534"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Zhong, W.-L., Qin, Y., Chen, S., and Sun, T. (2017). Antitumor Effect of Natural Product Molecules against Lung Cancer. A Global Scientific Vision\u2014Prevention, Diagnosis, and Treatment of Lung Cancer, IntechOpen.","DOI":"10.5772\/67241"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"8657","DOI":"10.2147\/JIR.S521756","article-title":"Amentoflavone Impedes NF-\u03baB Activation and Mediates Apoptosis Induction in Lung Cancer Cells: An in vitro and in silico exploration","volume":"18","author":"Faiyaz","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Soares, B.C.C., Khine, H.E.E., Sritularak, B., Chanvorachote, P., Alduina, R., Sungthong, R., and Chaotham, C. (2024). Cymensifin A: A promising pharmaceutical candidate to defeat lung cancer via cellular reactive oxygen species-mediated apoptosis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1361085"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"112933","DOI":"10.1016\/j.intimp.2024.112933","article-title":"Natural compound phloretin restores periodontal immune homeostasis via HIF-1\u03b1-regulated PI3K\/Akt and glycolysis in macrophages","volume":"141","author":"Zeng","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.joim.2024.05.004","article-title":"Cycloastragenol induces apoptosis and protective autophagy through AMPK\/ULK1\/mTOR axis in human non-small cell lung cancer cell lines","volume":"22","author":"Zhu","year":"2024","journal-title":"J. Integr. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1021\/acs.molpharmaceut.9b00943","article-title":"Cancer targeted gene therapy for inhibition of melanoma lung metastasis with eIF3i shRNA loaded liposomes","volume":"17","author":"Xiao","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2313366","DOI":"10.1080\/13510002.2024.2313366","article-title":"Jaceosidin induces apoptosis and inhibits migration in AGS gastric cancer cells by regulating ROS-mediated signaling pathways","volume":"29","author":"Liu","year":"2024","journal-title":"Redox Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"230145","DOI":"10.1183\/16000617.0145-2023","article-title":"CDK4\/6 inhibitors in lung cancer: Current practice and future directions","volume":"33","author":"Lv","year":"2024","journal-title":"Eur. Respir. Rev."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Singla, R.K., Sharma, P., Kumar, D., Gautam, R.K., Goyal, R., Tsagkaris, C., Dubey, A.K., Bansal, H., Sharma, R., and Shen, B. (2022). The role of nanomaterials in enhancing natural product translational potential and modulating endoplasmic reticulum stress in the treatment of ovarian cancer. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.987088"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1002\/tox.24475","article-title":"Intervention of a Communication Between PI3K\/Akt and \u03b2-Catenin by (\u2212)-Epigallocatechin-3-Gallate Suppresses TGF-\u03b21-Promoted Epithelial-Mesenchymal Transition and Invasive Phenotype of NSCLC Cells","volume":"40","author":"Hsu","year":"2025","journal-title":"Environ. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Huang, X., Arjsri, P., Srisawad, K., Umsumarng, S., Yodkeeree, S., and Dejkriengkraikul, P. (2025). Targeting MAPK Signaling: Loureirins A and B from Dracaena Loureiri Inhibit Epithelial\u2013Mesenchymal Transition and Invasion in Non-Small Cell Lung Cancer Cell Lines. Life, 15.","DOI":"10.3390\/life15030396"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Soddaen, P., Chairatvit, K., Pitchakarn, P., Laowanitwattana, T., Imsumran, A., and Wongnoppavich, A. (2025). Eurycomanone Blocks TGF-\u03b21-Induced Epithelial-to-Mesenchymal Transition, Migration, and Invasion Pathways in Human Non-Small Cell Lung Cancer Cells by Targeting Smad and Non-Smad Signaling. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157120"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1038\/s41598-025-88869-6","article-title":"3,5,6,7,8,3\u2032,4\u2032- Heptamethoxyflavonoid inhibits TGF-\u03b21-induced epithelial\u2013mesenchymal transition by regulating oxidative stress and autophagy through MEK\/ERK\/PI3K\/AKT\/mTOR signaling pathway","volume":"15","author":"Wang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Rana, J.N., Gul, K., and Mumtaz, S. (2025). Isorhamnetin: Reviewing Recent Developments in Anticancer Mechanisms and Nanoformulation-Driven Delivery. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157381"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"154612","DOI":"10.1016\/j.phymed.2022.154612","article-title":"Natural products targeting macrophages in tumor microenvironment are a source of potential antitumor agents","volume":"109","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"113096","DOI":"10.1016\/j.biopha.2022.113096","article-title":"Natural compounds: A new perspective on targeting polarization and infiltration of tumor-associated macrophages in lung cancer","volume":"151","author":"Zhou","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"156093","DOI":"10.1016\/j.phymed.2024.156093","article-title":"Liposomal honokiol inhibits non-small cell lung cancer progression and enhances PD-1 blockade via suppressing M2 macrophages polarization","volume":"135","author":"Cheng","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"157085","DOI":"10.1016\/j.phymed.2025.157085","article-title":"Artesunate modulates the tumor microenvironment via STAT1\/IRF1-mediated TAM repolarization and T cell activation in non-small cell lung cancer","volume":"146","author":"Hu","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"106988","DOI":"10.1016\/j.phrs.2023.106988","article-title":"Ginsenoside Rh2 augmented anti-PD-L1 immunotherapy by reinvigorating CD8+ T cells via increasing intratumoral CXCL10","volume":"198","author":"Huang","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"154968","DOI":"10.1016\/j.phymed.2023.154968","article-title":"Blocking LTB4 signaling-mediated TAMs recruitment by Rhizoma Coptidis sensitizes lung cancer to immunotherapy","volume":"119","author":"Yan","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Liu, B.-N., Chen, J., and Piao, Y. (2024). Global research and emerging trends in autophagy in lung cancer: A bibliometric and visualized study from 2013 to 2022. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1352422"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s11030-018-9903-7","article-title":"Synthesis and biological evaluation of benzomorpholine derivatives as novel EZH2 inhibitors for anti-non-small cell lung cancer activity","volume":"23","author":"Feng","year":"2019","journal-title":"Mol. Divers."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e33934","DOI":"10.1016\/j.heliyon.2024.e33934","article-title":"Targeting ferroptosis regulators in lung cancer: Exploring natural products","volume":"10","author":"Yuhao","year":"2024","journal-title":"Heliyon"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"149274","DOI":"10.1016\/j.bbrc.2023.149274","article-title":"Gigantol exerts anti-lung cancer activity by inducing ferroptosis via SLC7A11-GPX4 axis","volume":"690","author":"Chen","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/tox.23857","article-title":"Butyrate enhances erastin-induced ferroptosis of lung cancer cells via modulating the ATF3\/SLC7A11 pathway","volume":"39","author":"Bi","year":"2023","journal-title":"Environ. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Ni, Y., Liu, J., Zeng, L., Yang, Y., Liu, L., Yao, M., Chai, L., Zhang, L., Li, Y., and Zhang, L. (2023). Natural product manoalide promotes EGFR-TKI sensitivity of lung cancer cells by KRAS-ERK pathway and mitochondrial Ca2+ overload-induced ferroptosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1109822"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"15593258211033114","DOI":"10.1177\/15593258211033114","article-title":"Diallyl Disulfide Attenuates Ionizing Radiation-Induced Migration and Invasion by Suppressing Nrf2 Signaling in Non\u2013small-Cell Lung Cancer","volume":"19","author":"Xu","year":"2021","journal-title":"Dose-Response"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s12032-024-02317-5","article-title":"Ferroptosis is an effective strategy for cancer therapy","volume":"41","author":"Khan","year":"2024","journal-title":"Med. Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Li, H., Lin, J., Yang, F., Deng, J., Lai, J., Zeng, J., Zou, W., Jiang, N., Huang, Q., and Li, H. (2022). Sanguisorba officinalis L. suppresses non-small cell lung cancer via downregulating the PI3K\/AKT\/mTOR signaling pathway based on network pharmacology and experimental investigation. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1054803"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"109030","DOI":"10.1016\/j.intimp.2022.109030","article-title":"Zoledronic acid enhances the efficacy of immunotherapy in non-small cell lung cancer","volume":"110","author":"Zheng","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"109598","DOI":"10.1016\/j.biopha.2019.109598","article-title":"Penfluridol: An antipsychotic agent suppresses lung cancer cell growth and metastasis by inducing G0\/G1 arrest and apoptosis","volume":"121","author":"Xue","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Malla, R., Viswanathan, S., Makena, S., Kapoor, S., Verma, D., Raju, A.A., Dunna, M., and Muniraj, N. (2024). Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing. Cancers, 16.","DOI":"10.3390\/cancers16081463"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/s41416-023-02502-9","article-title":"Unlocking hidden potential: Advancements, approaches, and obstacles in repurposing drugs for cancer therapy","volume":"130","author":"Weth","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-024-01808-1","article-title":"Drug repurposing for cancer therapy","volume":"9","author":"Xia","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1097\/CAD.0000000000000875","article-title":"Metformin mediated microRNA-7 upregulation inhibits growth, migration, and invasion of non-small cell lung cancer A549 cells","volume":"31","author":"Dong","year":"2020","journal-title":"Anti-Cancer Drugs"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wang, Y., Hu, Y., Wang, T., Che, G., and Li, L. (2023). Addition of metformin for non-small cell lung cancer patients receiving antineoplastic agents. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1123834"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41416-023-02204-2","article-title":"Is it still worth pursuing the repurposing of metformin as a cancer therapeutic?","volume":"128","author":"Lord","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"118507","DOI":"10.1016\/j.biopha.2025.118507","article-title":"From basics to clinics: New opportunities for metformin in tumor metabolic intervention and treatment","volume":"191","author":"Lv","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Feng, Q., Huo, C., Wang, M., Huang, H., Zheng, X., and Xie, M. (2024). Research progress on cuproptosis in cancer. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1290592"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"107912","DOI":"10.1016\/j.phrs.2025.107912","article-title":"Statin drugs and lipid modulation: Mechanistic basis considering lipid rafts, kinase signaling, myopathy, and cancer","volume":"220","author":"Karthikeyan","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1038\/s12276-023-01079-w","article-title":"Functional significance of cholesterol metabolism in cancer: From threat to treatment","volume":"55","author":"Xiao","year":"2023","journal-title":"Exp. Mol. Med."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Halcrow, P.W., Geiger, J.D., and Chen, X. (2021). Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.627639"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Kannappan, V., Ali, M., Small, B., Rajendran, G., Elzhenni, S., Taj, H., Wang, W., and Dou, Q.P. (2021). Recent Advances in Repurposing Disulfiram and Disulfiram Derivatives as Copper-Dependent Anticancer Agents. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.741316"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.3892\/ol.2017.6325","article-title":"Repurposing itraconazole as an anticancer agent","volume":"14","author":"Tsubamoto","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1021\/acs.jmedchem.3c01432","article-title":"Identification of a Dual Autophagy and REV-ERB Inhibitor with in Vivo Anticancer Efficacy","volume":"67","author":"Palomba","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5831","DOI":"10.1039\/D3BM00601H","article-title":"GPX4 inhibition synergistically boosts mitochondria targeting nanoartemisinin-induced apoptosis\/ferroptosis combination cancer therapy","volume":"11","author":"Yu","year":"2023","journal-title":"Biomater. Sci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"123248","DOI":"10.1016\/j.ijpharm.2023.123248","article-title":"A biodegradable hollow nanoagent enables a boosted chemodynamic therapy by simultaneous autophagy inhibition and macrophage reeducation","volume":"643","author":"Zhu","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.etap.2017.12.004","article-title":"The selectivity of artemisinin-based drugs on human lung normal and cancer cells","volume":"57","author":"Li","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"104809","DOI":"10.1016\/j.neubiorev.2022.104809","article-title":"Treatment of cancer with antipsychotic medications: Pushing the boundaries of schizophrenia and cancer","volume":"141","author":"Brown","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e181","DOI":"10.1038\/cddis.2011.62","article-title":"Chemosensitization by phenothiazines in human lung cancer cells: Impaired resolution of \u03b3H2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation","volume":"2","author":"Zong","year":"2011","journal-title":"Cell Death Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1111\/bcp.15155","article-title":"Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis","volume":"88","author":"Wu","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Xu, X., Zhang, S., Xu, T., Zhan, M., Chen, C., and Zhang, C. (2022). Efficacy and Safety of Bevacizumab Biosimilars Compared With Reference Biologics in Advanced Non-small Cell Lung Cancer or Metastatic Colorectal Cancer Patients: A Network Meta-Analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.880090"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Hou, Y., Li, H., Zhu, L., Li, Y., Zeng, Y., Quan, T., Xiang, Z., Zhang, Y., Bian, Y., and Wei, Y. (2025). A review of natural compounds to regulate platelet aggregation: Molecular mechanism and research advance. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1537776"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5106","DOI":"10.1016\/j.apsb.2024.10.015","article-title":"Recent advances in reactive oxygen species (ROS)-responsive drug delivery systems for photodynamic therapy of cancer","volume":"14","author":"Hu","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.tips.2023.12.005","article-title":"Context-dependent role of SIRT3 in cancer","volume":"45","author":"Zhang","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e33463","DOI":"10.1097\/MD.0000000000033463","article-title":"The effect of ginsenoside Rg3 combined with chemotherapy on immune function in non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials","volume":"102","author":"Gao","year":"2023","journal-title":"Medicine"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Peng, Z., Wu, W.W., and Yi, P. (2021). The Efficacy of Ginsenoside Rg3 Combined with First-line Chemotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer in China: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.630825"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"7826753","DOI":"10.1155\/2016\/7826753","article-title":"Ginsenoside Rg3 Serves as an Adjuvant Chemotherapeutic Agent and VEGF Inhibitor in the Treatment of Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review","volume":"2016","author":"Xu","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Sun, X.-Y., Jia, L.-Y., Rong, Z., Zhou, X., Cao, L.-Q., Li, A.-H., Guo, M., Jin, J., Wang, Y.-D., and Huang, L. (2022). Research Advances on Matrine. Front. Chem., 10.","DOI":"10.3389\/fchem.2022.867318"},{"key":"ref_152","first-page":"14701","article-title":"Matrine promotes the efficacy and safety of platinum-based doublet chemotherapy for advanced non-small cell lung cancer","volume":"8","author":"Rong","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s10616-009-9211-2","article-title":"Effects of matrine against the growth of human lung cancer and hepatoma cells as well as lung cancer cell migration","volume":"59","author":"Zhang","year":"2009","journal-title":"Cytotechnology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s10637-021-01179-2","article-title":"A phase I study of the tyrosine kinase inhibitor anlotinib combined with platinum\/pemetrexed-based chemotherapy in untreated nonsquamous non-small-cell lung cancer","volume":"40","author":"Huang","year":"2021","journal-title":"Investig. New Drugs"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"110937","DOI":"10.1016\/j.intimp.2023.110937","article-title":"Association between pretreatment C-reactive protein level and survival in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis","volume":"124","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Tian, W., Ning, J., Chen, L., Zeng, Y., Shi, Y., Xiao, G., He, S., Tanzhu, G., and Zhou, R. (2024). Cost-effectiveness of tumor-treating fields plus standard therapy for advanced non-small cell lung cancer progressed after platinum-based therapy in the United States. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1333128"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1097\/JTO.0b013e318262de4a","article-title":"A phase I study of erlotinib and hydroxychloroquine in advanced non\u2013small-cell lung cancer","volume":"7","author":"Goldberg","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"101945","DOI":"10.1016\/j.tranon.2024.101945","article-title":"Metformin as anticancer agent and adjuvant in cancer combination therapy: Current progress and future prospect","volume":"44","author":"Zhu","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"690","DOI":"10.5732\/cjc.011.10056","article-title":"Chloroquine enhances the cytotoxicity of topotecan by inhibiting autophagy in lung cancer cells","volume":"30","author":"Wang","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e7049","DOI":"10.1002\/cam4.7049","article-title":"Cardiovascular\/anti-inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta-analysis of randomized trials","volume":"13","author":"Benjamin","year":"2024","journal-title":"Cancer Med."},{"key":"ref_161","first-page":"100150","article-title":"A pooled analysis of two phase II trials evaluating metformin plus platinum-based chemotherapy in advanced non-small cell lung cancer","volume":"20","author":"Parikh","year":"2019","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_162","first-page":"100158","article-title":"Phase Ib\/II study of hydroxychloroquine in combination with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC)","volume":"21","author":"Malhotra","year":"2019","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Agalakova, N.I. (2024). Chloroquine and Chemotherapeutic Compounds in Experimental Cancer Treatment. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020945"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"154723","DOI":"10.1016\/j.phymed.2023.154723","article-title":"Shenlingcao oral liquid for patients with non-small cell lung cancer receiving adjuvant chemotherapy after radical resection: A multicenter randomized controlled trial","volume":"113","author":"Liu","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"e838","DOI":"10.1038\/cddis.2013.350","article-title":"Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment","volume":"4","author":"Sui","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3762\/bjnano.16.24","article-title":"Graphene oxide\u2013chloroquine conjugate induces DNA damage in A549 lung cancer cells through autophagy modulation","volume":"16","author":"Arya","year":"2025","journal-title":"Beilstein J. Nanotechnol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"7775","DOI":"10.2147\/IJN.S474158","article-title":"Construction and Evaluation of BAL-PTX Co-Loaded Lipid Nanosystem for Promoting the Anti-Lung Cancer Efficacy of Paclitaxel and Reducing the Toxicity of Chemotherapeutic Drugs","volume":"19","author":"Chen","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1007\/s11033-021-06187-2","article-title":"Insights into the antitumor mechanism of ginsenosides Rg3","volume":"48","author":"Liu","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"750","DOI":"10.3892\/ol.2021.13011","article-title":"Progress on the study of the anticancer effects of artesunate (Review)","volume":"22","author":"Yang","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3736\/jcim20080206","article-title":"Artesunate combined with vinorelbine plus cisplatin in treatment of advanced non-small cell lung cancer: A randomized controlled trial","volume":"6","author":"Zhang","year":"2008","journal-title":"J. Chin. Integr. Med."},{"key":"ref_171","first-page":"907","article-title":"Carnosic acid enhances the anti-lung cancer effect of cisplatin by inhibiting myeloid-derived suppressor cells","volume":"16","author":"Liu","year":"2018","journal-title":"Chin. J. Nat. Med."},{"key":"ref_172","first-page":"3828","article-title":"Resveratrol-mediated ADAM9 degradation decreases cancer progression and provides synergistic effects in combination with chemotherapy","volume":"10","author":"Lin","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1093\/jpp\/rgaf007","article-title":"Updated progression of honokiol in lung cancer treatment","volume":"77","author":"Gao","year":"2025","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1016\/j.ejca.2005.05.009","article-title":"Curcumin: The story so far","volume":"41","author":"Sharma","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1186\/s13046-019-1234-8","article-title":"Curcumin overcome primary gefitinib resistance in non-small-cell lung cancer cells through inducing autophagy-related cell death","volume":"38","author":"Chen","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_176","first-page":"137","article-title":"Curcumin Lowers Erlotinib Resistance in Non-Small Cell Lung Carcinoma Cells With Mutated EGF Receptor","volume":"21","author":"Li","year":"2014","journal-title":"Oncol. Res. Featur. Preclin. Clin. Cancer Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12951-023-02099-4","article-title":"Targeted co-delivery of curcumin and erlotinib by MoS2 nanosheets for the combination of synergetic chemotherapy and photothermal therapy of lung cancer","volume":"21","author":"Chen","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.bcp.2012.07.018","article-title":"Berberine: New perspectives for old remedies","volume":"84","author":"Tillhon","year":"2012","journal-title":"Biochem. Pharmacol."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"105998","DOI":"10.1016\/j.phrs.2021.105998","article-title":"The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition","volume":"175","author":"Chen","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"103365","DOI":"10.1016\/j.tice.2026.103365","article-title":"Overcoming osimertinib resistance in NSCLC: The role of Notch1 pathway inhibition by berberine","volume":"100","author":"Jiang","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.2147\/IJN.S460047","article-title":"Biopolymer-based nanomedicine for cancer therapy: Opportunities and challenges","volume":"19","author":"Wu","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1016\/j.apsb.2024.06.003","article-title":"In situ tumor vaccine with optimized nanoadjuvants and lymph node targeting capacity to treat ovarian cancer and metastases","volume":"14","author":"Li","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.21037\/tlcr-2025-524","article-title":"Targeting arachidonic acid-modulated autophagy: A novel axis in crizotinib resistance","volume":"14","author":"Tahir","year":"2025","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41392-022-01168-8","article-title":"Protein tyrosine kinase inhibitor resistance in malignant tumors: Molecular mechanisms and future perspective","volume":"7","author":"Yang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"1","DOI":"10.20517\/cdr.2024.151","article-title":"Ferroptosis-related signaling pathways in cancer drug resistance","volume":"8","author":"Yang","year":"2025","journal-title":"Cancer Drug Resist."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.21037\/tlcr-20-1153","article-title":"Concurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer\u2014An option for overcoming EGFR-TKI resistance","volume":"10","author":"Han","year":"2021","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"6967","DOI":"10.1158\/1078-0432.CCR-19-0437","article-title":"Combination of metformin and gefitinib as first-line therapy for nondiabetic advanced NSCLC patients with EGFR mutations: A randomized, double-blind phase II trial","volume":"25","author":"Li","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"e192553","DOI":"10.1001\/jamaoncol.2019.2553","article-title":"Effect of metformin plus tyrosine kinase inhibitors compared with tyrosine kinase inhibitors alone in patients with epidermal growth factor receptor\u2013mutated lung adenocarcinoma: A phase 2 randomized clinical trial","volume":"5","author":"Arrieta","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Neal, J.W., Wakelee, H.A., Feliciano, J.L., Goldberg, S.B., Morgensztern, D., Das, M.S., Heist, R.S., Lennes, I.T., Muzikansky, A., and Edelman, M.J.X. (2014). A Multicenter Randomized Phase II Trial of Erlotinib with and Without Hydroxychloroquine (HCQ) in TKI-Naive Patients (pts) with Epidermal Growth Factor Receptor (EGFR) Mutant Advanced Non-Small Cell Lung Cancer (NSCLC), American Society of Clinical Oncology.","DOI":"10.1200\/jco.2014.32.15_suppl.8088"},{"key":"ref_190","first-page":"421","article-title":"Progression of Central Nervous System Metastases in Advanced Nonsmall Cell Lung Cancer Patients Effectively Treated with First-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor","volume":"33","author":"Yu","year":"2018","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41392-024-01772-w","article-title":"Targeting carnitine palmitoyl transferase 1A (CPT1A) induces ferroptosis and synergizes with immunotherapy in lung cancer","volume":"9","author":"Ma","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"157741","DOI":"10.1016\/j.phymed.2025.157741","article-title":"Tougu Xiaotong capsules inhibit lung cancer and gefitinib-resistant cells by blocking ERBB2\/PI3K-AKT-mTOR signaling and triggering ferroptosis","volume":"150","author":"Ni","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"106739","DOI":"10.1016\/j.phrs.2023.106739","article-title":"B-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer","volume":"191","author":"Xu","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.2147\/IJN.S488213","article-title":"A Novel Systemic siDR6 Delivery System Based on DP7-C for the Treatment of Metastatic Lung Cancer","volume":"20","author":"Zhou","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_195","doi-asserted-by":"crossref","unstructured":"Mu, X., and Li, Y. (2024). Case report: Therapeutic response to lorlatinib in advanced large-cell neuroendocrine carcinoma of the lung and breast cancer: A heterochronous double malignancy perspective. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1413897"},{"key":"ref_196","doi-asserted-by":"crossref","unstructured":"Wang, Y., Hu, J., Fleishman, J.S., Li, Y., Ren, Z., Wang, J., Feng, Y., Chen, J., and Wang, H. (2024). Inducing ferroptosis by traditional medicines: A novel approach to reverse chemoresistance in lung cancer. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1290183"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ijpharm.2019.04.078","article-title":"Liposome mediated-CYP1A1 gene silencing nanomedicine prepared using lipid film-coated proliposomes as a potential treatment strategy of lung cancer","volume":"566","author":"Zhang","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1007\/s13277-014-2996-4","article-title":"Curcumin reverses cisplatin resistance in cisplatin-resistant lung caner cells by inhibiting FA\/BRCA pathway","volume":"36","author":"Chen","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"201","DOI":"10.24966\/ACIM-7562\/100201","article-title":"Use of Curcumin with Tyrosine Kinase Inhibitors in EGFR-mutant Non-Small Cell Lung Cancer. A Phase I prospective Cohort Trial","volume":"7","author":"Kasymjanova","year":"2021","journal-title":"J. Altern. Complement. Integr. Med."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12943-022-01662-1","article-title":"Costunolide is a dual inhibitor of MEK1 and AKT1\/2 that overcomes osimertinib resistance in lung cancer","volume":"21","author":"Tian","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Kim, D.Y., and Choi, B.Y. (2019). Costunolide\u2014A Bioactive Sesquiterpene Lactone with Diverse Therapeutic Potential. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122926"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"10888","DOI":"10.3390\/ijms160510888","article-title":"Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone","volume":"16","author":"Lin","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"113417","DOI":"10.1016\/j.celrep.2023.113417","article-title":"Inhibiting G6PD by quercetin promotes degradation of EGFR T790M mutation","volume":"42","author":"Ge","year":"2023","journal-title":"Cell Rep."},{"key":"ref_204","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.2147\/IJN.S401570","article-title":"Promising Nanomedicines of Shikonin for Cancer Therapy","volume":"18","author":"Yan","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/s13346-024-01602-0","article-title":"Wheat germ agglutinin modified mixed micelles overcome the dual barrier of mucus\/enterocytes for effective oral absorption of shikonin and gefitinib","volume":"15","author":"Hou","year":"2024","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Salehi, B., Venditti, A., Sharifi-Rad, M., Kr\u0119giel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E.B., and Novellino, E. (2019). The Therapeutic Potential of Apigenin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061305"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Chen, Z., Tian, D., Liao, X., Zhang, Y., Xiao, J., Chen, W., Liu, Q., Chen, Y., Li, D., and Zhu, L. (2019). Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1\u03b1, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00260"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s12032-007-9015-1","article-title":"Selective COX-2 inhibitor celecoxib combined with EGFR-TKI ZD1839 on non-small cell lung cancer cell lines: In vitro toxicity and mechanism study","volume":"25","author":"Chen","year":"2008","journal-title":"Med. Oncol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1002\/cncr.29480","article-title":"Randomized phase 2 trial of erlotinib in combination with high-dose celecoxib or placebo in patients with advanced non-small cell lung cancer","volume":"121","author":"Reckamp","year":"2015","journal-title":"Cancer"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1158\/1078-0432.CCR-06-0112","article-title":"A Phase I Trial to Determine the Optimal Biological Dose of Celecoxib when Combined with Erlotinib in Advanced Non\u2013Small Cell Lung Cancer","volume":"12","author":"Reckamp","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_212","first-page":"100229","article-title":"Repurposing loperamide to overcome gefitinib resistance by triggering apoptosis independent of autophagy induction in KRAS mutant NSCLC cells","volume":"25","author":"Tong","year":"2020","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1021\/acsptsci.3c00202","article-title":"Circumvention of Gefitinib Resistance by Repurposing Flunarizine via Histone Deacetylase Inhibition","volume":"6","author":"To","year":"2023","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"105007","DOI":"10.1016\/j.phrs.2020.105007","article-title":"Lymecycline reverses acquired EGFR-TKI resistance in non\u2013small-cell lung cancer by targeting GRB2","volume":"159","author":"Chen","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Suzuki, S., Yamamoto, M., Sanomachi, T., Togashi, K., Sugai, A., Seino, S., Okada, M., Yoshioka, T., and Kitanaka, C. (2020). Doxazosin, a Classic Alpha 1-Adrenoceptor Antagonist, Overcomes Osimertinib Resistance in Cancer Cells via the Upregulation of Autophagy as Drug Repurposing. Biomedicines, 8.","DOI":"10.3390\/biomedicines8080273"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"814","DOI":"10.18632\/oncotarget.2891","article-title":"Short-hairpin RNA library: Identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer","volume":"6","author":"Sudo","year":"2014","journal-title":"Oncotarget"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"117162","DOI":"10.1016\/j.bcp.2025.117162","article-title":"Glimepiride overcomes acquired resistance to EGFR TKIs in lung cancer via the AMPK\/ERK\/MMP7 signaling pathway","volume":"241","author":"Zhang","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"100888","DOI":"10.1016\/j.mcpro.2024.100888","article-title":"Global Proteomics Indicates Subcellular-Specific Anti-Ferroptotic Responses to Ionizing Radiation","volume":"24","author":"Christopher","year":"2025","journal-title":"Mol. Cell. Proteom."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.32604\/or.2025.065755","article-title":"The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance","volume":"33","author":"Verza","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"2303412","DOI":"10.1002\/adhm.202303412","article-title":"Glutathione Depletion-Induced Versatile Nanomedicine for Potentiating the Ferroptosis to Overcome Solid Tumor Radioresistance and Enhance Immunotherapy","volume":"13","author":"Song","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41401-024-01233-8","article-title":"Clobetasol propionate, a Nrf-2 inhibitor, sensitizes human lung cancer cells to radiation-induced killing via mitochondrial ROS-dependent ferroptosis","volume":"45","author":"Rai","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"681","DOI":"10.7150\/thno.88899","article-title":"NRF2 promotes radiation resistance by cooperating with TOPBP1 to activate the ATR-CHK1 signaling pathway","volume":"14","author":"Sun","year":"2024","journal-title":"Theranostics"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s11101-022-09833-0","article-title":"Recent advances in biosynthesis and pharmacology of \u03b2-elemene","volume":"22","author":"Chen","year":"2022","journal-title":"Phytochem. Rev."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1746-1596-9-68","article-title":"Enhancement of recombinant myricetin on the radiosensitivity of lung cancer A549 and H1299 cells","volume":"9","author":"Zhang","year":"2014","journal-title":"Diagn. Pathol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"111017","DOI":"10.1016\/j.biopha.2020.111017","article-title":"Myricetin: A review of the most recent research","volume":"134","author":"Song","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1002\/iub.2242","article-title":"Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p\/WEE1 axis","volume":"72","author":"Wang","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"102051","DOI":"10.1016\/j.adro.2026.102051","article-title":"Synergistic Effect of Linebacker-1 With Radiation Therapy in a Mouse Lung Cancer Model","volume":"11","author":"Richards","year":"2026","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1021\/acs.molpharmaceut.3c00869","article-title":"PDGFR\u03b2-Antagonistic Affibody-Mediated Tumor-Targeted Tumor Necrosis Factor-Alpha for Enhanced Radiotherapy in Lung Cancer","volume":"21","author":"Tang","year":"2024","journal-title":"Mol. Pharm."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Tian, F., Chen, Z., Zhou, D., and Mo, L. (2022). Prevalence of polypharmacy and potentially inappropriate medication use in older lung cancer patients: A systematic review and meta-analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1044885"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"9252","DOI":"10.1158\/0008-5472.CAN-06-1239","article-title":"Nelfinavir Down-regulates Hypoxia-Inducible Factor 1\u03b1 and VEGF Expression and Increases Tumor Oxygenation: Implications for Radiotherapy","volume":"66","author":"Pore","year":"2006","journal-title":"Cancer Res."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"132","DOI":"10.2174\/0125899775300432240625045414","article-title":"Radiosensitizing Effects of Metformin on Ionizing Irradiation: An Overview of Animal and Clinical Studies","volume":"17","author":"Haghighi","year":"2025","journal-title":"Curr. Drug Res. Rev."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"114981","DOI":"10.1016\/j.bcp.2022.114981","article-title":"Metformin increases the radiosensitivity of non-small cell lung cancer cells by destabilizing NRF2","volume":"199","author":"Sun","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.3892\/ol.2017.6372","article-title":"Niclosamide enhances the antitumor effects of radiation by inhibiting the hypoxia-inducible factor-1\u03b1\/vascular endothelial growth factor signaling pathway in human lung cancer cells","volume":"14","author":"Xiang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1158\/1535-7163.MCT-13-0608","article-title":"Disruption of STAT3 by Niclosamide Reverses Radioresistance of Human Lung Cancer","volume":"13","author":"You","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_235","first-page":"5959","article-title":"Inhibition of cyclooxygenase-2 sensitizes lung cancer cells to radiation-induced apoptosis","volume":"17","author":"Han","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ijrobp.2007.08.065","article-title":"Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism","volume":"70","author":"Dittmann","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"110122","DOI":"10.1016\/j.cellsig.2021.110122","article-title":"An overview on the biological activity and anti-cancer mechanism of lovastatin","volume":"87","author":"Xie","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/JTO.0b013e3182049d8b","article-title":"Lovastatin sensitizes lung cancer cells to ionizing radiation: Modulation of molecular pathways of radioresistance and tumor suppression","volume":"6","author":"Sanli","year":"2011","journal-title":"J. Thorac. Oncol."},{"key":"ref_239","first-page":"80","article-title":"Atorvastatin sensitizes breast and lung cancer cells to ionizing radiation","volume":"19","author":"Hosseinimehr","year":"2020","journal-title":"Iran. J. Pharm. Res. IJPR"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.jconrel.2023.09.044","article-title":"A redox-responsive nanosystem to suppress chemoresistant lung cancer through targeting STAT3","volume":"363","author":"Feng","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s10637-024-01451-1","article-title":"Radiosensitization effect of quinoline-indole-schiff base derivative 10E on non-small cell lung cancer cells in vitro and in tumor xenografts","volume":"42","author":"Liu","year":"2024","journal-title":"Investig. New Drugs"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"e1918070","DOI":"10.1001\/jamanetworkopen.2019.18070","article-title":"Effect of concurrent Chemoradiation with celecoxib vs concurrent Chemoradiation alone on survival among patients with non\u2013small cell lung cancer with and without cyclooxygenase 2 genetic variants: A phase 2 randomized clinical trial","volume":"2","author":"Bi","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.3892\/or_00000987","article-title":"Gimeracil, a component of S-1, may enhance the antitumor activity of X-ray irradiation in human cancer xenograft models in vivo","volume":"24","author":"Fukushima","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1001\/jamaoncol.2019.2095","article-title":"Clinical Outcomes of the HIV Protease Inhibitor Nelfinavir With Concurrent Chemoradiotherapy for Unresectable Stage IIIA\/IIIB Non\u2013Small Cell Lung Cancer","volume":"5","author":"Rengan","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_245","first-page":"100149","article-title":"Disulfiram alone regulates the radiosensitivity of lung cancer through NF-\u03baB pathway and regulates the immune microenvironment after radiotherapy by targeting PD-L1 through c-Myc","volume":"15","author":"Cui","year":"2025","journal-title":"Adv. Cancer Biol."},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Fu, Y., Zheng, Y., Wang, P.-P., Chen, Y.-Y., and Ding, Z.-Y. (2022). Immunotherapy for a POLE Mutation Advanced Non-Small-Cell Lung Cancer Patient. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.817265"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"107296","DOI":"10.1016\/j.intimp.2020.107296","article-title":"Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer","volume":"91","author":"Zhou","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_248","first-page":"82","article-title":"Role of PD-1\/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy","volume":"11","author":"Godiyal","year":"2024","journal-title":"Mil. Med. Res."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Nath, L.R., Sethi, G., and Liju, V.B. (2025). Editorial: Immunomodulatory molecules of natural origin: Innovative strategies for combatting cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1568568"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"101357","DOI":"10.1016\/j.xcrm.2023.101357","article-title":"Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3","volume":"5","author":"Wang","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"216568","DOI":"10.1016\/j.canlet.2023.216568","article-title":"Blocking MARCO+ tumor-associated macrophages improves anti-PD-L1 therapy of hepatocellular carcinoma by promoting the activation of STING-IFN type I pathway","volume":"582","author":"Ding","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"216726","DOI":"10.1016\/j.canlet.2024.216726","article-title":"PD-1 regulation in immune homeostasis and immunotherapy","volume":"588","author":"Gao","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"398","DOI":"10.21037\/tlcr-23-144","article-title":"Immunotherapy for advanced non-small cell lung cancer with negative programmed death-ligand 1 expression: A literature review","volume":"13","author":"Bai","year":"2024","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12943-024-01976-2","article-title":"rs822336 binding to C\/EBP\u03b2 and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1\/PD-L1 therapy in advanced NSCLC","volume":"23","author":"Polcaro","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Tian, F., Chen, Z., Tang, R., Feng, Q., and Wu, F. (2022). Impact of the expert consensus on polypharmacy and potentially inappropriate medication use in elderly lung cancer outpatients with multimorbidity: An interrupted time series analysis, 2016\u20132021. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.992394"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"694","DOI":"10.2174\/1871527319666200722153611","article-title":"Prospective function of different antioxidant containing natural products in the treatment of neurodegenerative diseases","volume":"20","author":"Rahman","year":"2021","journal-title":"CNS Neurol. Disord.-Drug Targets-CNS Neurol. Disord."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"e27576","DOI":"10.1016\/j.heliyon.2024.e27576","article-title":"Dual immunotherapy in advanced or metastatic non-small cell lung cancer: A network meta-analysis","volume":"10","author":"Yang","year":"2024","journal-title":"Heliyon"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"158272","DOI":"10.1016\/j.phymed.2026.158272","article-title":"Ginsenoside Rg3 improves atezolizumab immune checkpoint therapy in triple-negative breast cancer by targeting FUT8-mediated PD-L1 N-glycosylation","volume":"156","author":"Tian","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_259","doi-asserted-by":"crossref","unstructured":"Wang, W., Kong, M., Shen, F., Li, P., Chen, C., Li, Y., Li, C., Qian, Z., Zhong, A., and Wang, Y. (2024). Ginsenoside Rg3 targets glycosylation of PD-L1 to enhance anti-tumor immunity in non-small cell lung cancer. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1434078"},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcp.2018.12.001","article-title":"Ginsenoside Rb1 and mitochondria: A short review of the literature","volume":"43","author":"Zhou","year":"2019","journal-title":"Mol. Cell. Probes"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.brainresbull.2016.04.002","article-title":"Ginsenoside Rb1 as a neuroprotective agent: A review","volume":"125","author":"Ahmed","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1186\/s12951-025-03456-1","article-title":"Overcoming acquired immunotherapy resistance in non-small cell lung cancer using ginsenoside Rb1-loaded, peptide-enhanced exosome delivery systems","volume":"23","author":"Jin","year":"2025","journal-title":"J. Nanobiotechnol."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"157649","DOI":"10.1016\/j.phymed.2025.157649","article-title":"Ginsenoside F3 alleviates T cell exhaustion via RIPOR2-mediated immunometabolic reprogramming to potentiate anti-PD-1 therapy","volume":"150","author":"Jiang","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"106206","DOI":"10.1016\/j.intimp.2020.106206","article-title":"Andrographolide potentiates PD-1 blockade immunotherapy by inhibiting COX2-mediated PGE2 release","volume":"81","author":"Liu","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"106198","DOI":"10.1016\/j.phrs.2022.106198","article-title":"Andrographolide suppresses non-small-cell lung cancer progression through induction of autophagy and antitumor immune response","volume":"179","author":"Wang","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"6197","DOI":"10.2174\/0929867329666220324143215","article-title":"Current Overview on the Potency of Natural Products for Modulating Myeloid-derived Suppressor Cells Dependent Cold Tumors","volume":"29","author":"Malla","year":"2022","journal-title":"Curr. Med. Chem."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1186\/s12951-026-04216-5","article-title":"CD93-targeted resveratrol-loaded PLGA nanoparticles remodel CD8+ T cell metabolism through AIF-mediated oxidative phosphorylation to overcome lung cancer immunotherapy resistance","volume":"24","author":"Jiang","year":"2026","journal-title":"J. Nanobiotechnol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"117863","DOI":"10.1016\/j.bcp.2026.117863","article-title":"A resveratrol derivative RVX-208 inhibits PD-1\/PD-L1 to restrain non-small cell lung cancer as an immunotherapy","volume":"249","author":"Chen","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.1021\/acs.molpharmaceut.3c00427","article-title":"Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted \u03b1-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response","volume":"20","author":"Qin","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"112152","DOI":"10.1016\/j.intimp.2024.112152","article-title":"The real-world treatment characteristic and efficacy of immune checkpoint inhibitors in non-small cell lung cancer: Data from a retrospective cohort study","volume":"134","author":"Zhang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1200\/JCO.23.00980","article-title":"Canakinumab versus placebo in combination with first-line pembrolizumab plus chemotherapy for advanced non\u2013small-cell lung cancer: Results from the CANOPY-1 trial","volume":"42","author":"Tan","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ccell.2019.06.008","article-title":"Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1\/PD-L1 therapeutic efficacy","volume":"36","author":"Lee","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"114940","DOI":"10.1016\/j.bcp.2022.114940","article-title":"Myricetin inhibits interferon-\u03b3-induced PD-L1 and IDO1 expression in lung cancer cells","volume":"197","author":"Chen","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41379-018-0160-1","article-title":"Differential expression of PD-L1 and IDO1 in association with the immune microenvironment in resected lung adenocarcinomas","volume":"32","author":"Zhang","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_275","first-page":"517","article-title":"Nagilactone E increases PD-L1 expression through activation of c-Jun in lung cancer cells","volume":"18","author":"Chen","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.2217\/fon-2020-1098","article-title":"Canakinumab with and Without Pembrolizumab in Patients with Resectable Non-Small-Cell Lung Cancer: CANOPY-N Study Design","volume":"17","author":"Garrido","year":"2021","journal-title":"Future Oncol."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.21037\/tlcr-20-1072","article-title":"Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2","volume":"9","author":"Huang","year":"2020","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1158\/1078-0432.CCR-12-2777","article-title":"Synergistic effects of metformin treatment in combination with gefitinib, a selective EGFR tyrosine kinase inhibitor, in LKB1 wild-type NSCLC cell lines","volume":"19","author":"Morgillo","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1158\/1078-0432.CCR-13-2613","article-title":"Metformin sensitizes EGFR-TKI\u2013resistant human lung cancer cells in vitro and in vivo through inhibition of IL-6 signaling and EMT reversal","volume":"20","author":"Li","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1038\/bjc.2013.187","article-title":"Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK","volume":"108","author":"Storozhuk","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1001\/jamaoncol.2021.2318","article-title":"Addition of metformin to concurrent chemoradiation in patients with locally advanced non\u2013small cell lung cancer: The NRG-LU001 phase 2 randomized clinical trial","volume":"7","author":"Skinner","year":"2021","journal-title":"JAMA Oncol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s13046-018-0938-5","article-title":"Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_285","doi-asserted-by":"crossref","unstructured":"Han, W., Pan, H., Chen, Y., Sun, J., Wang, Y., Li, J., Ge, W., Feng, L., Lin, X., and Wang, X. (2011). EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018691"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/JTO.0b013e31828c7210","article-title":"The autophagy inhibitor chloroquine overcomes the innate resistance of wild-type EGFR non-small-cell lung cancer cells to erlotinib","volume":"8","author":"Zou","year":"2013","journal-title":"J. Thorac. Oncol."},{"key":"ref_287","doi-asserted-by":"crossref","unstructured":"Tang, M.-C., Wu, M.-Y., Hwang, M.-H., Chang, Y.-T., Huang, H.-J., Lin, A.M.-Y., and Yang, J.C.-H. (2015). Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0119135"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.18632\/oncotarget.2017","article-title":"Combining AKT inhibition with chloroquine and gefitinib prevents compensatory autophagy and induces cell death in EGFR mutated NSCLC cells","volume":"5","author":"Bokobza","year":"2014","journal-title":"Oncotarget"},{"key":"ref_289","doi-asserted-by":"crossref","unstructured":"Ye, H., Chen, M., Cao, F., Huang, H., Zhan, R., and Zheng, X. (2016). Chloroquine, an autophagy inhibitor, potentiates the radiosensitivity of glioma initiating cells by inhibiting autophagy and activating apoptosis. BMC Neurol., 16.","DOI":"10.1186\/s12883-016-0700-6"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1159\/000486222","article-title":"Chloroquine enhances the radiosensitivity of bladder cancer cells by inhibiting autophagy and activating apoptosis","volume":"45","author":"Wang","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_291","doi-asserted-by":"crossref","unstructured":"Firat, E., Weyerbrock, A., Gaedicke, S., Grosu, A.-L., and Niedermann, G. (2012). Chloroquine or chloroquine-PI3K\/Akt pathway inhibitor combinations strongly promote \u03b3-irradiation-induced cell death in primary stem-like glioma cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047357"},{"key":"ref_292","first-page":"1835","article-title":"Introduction to the guidance for industry on liposome drug products: Chemistry, manufacturing, and controls; human pharmacokinetics and bioavailability; and labeling documentation issued by FDA","volume":"27","author":"Zhou","year":"2018","journal-title":"Chin. J. New Drugs"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.2147\/IJN.S306831","article-title":"Design and characterization of spray-dried proliposomes for the pulmonary delivery of curcumin","volume":"16","author":"Adel","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ijpharm.2018.09.050","article-title":"Utilizing glutathione-triggered nanoparticles to enhance chemotherapy of lung cancer by reprograming the tumor microenvironment","volume":"552","author":"Cui","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"113801","DOI":"10.1016\/j.addr.2021.05.011","article-title":"Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies","volume":"175","author":"Tong","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.ejps.2013.03.009","article-title":"Quercetin solid lipid microparticles: A flavonoid for inhalation lung delivery","volume":"49","author":"Scalia","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"114083","DOI":"10.1016\/j.addr.2021.114083","article-title":"Clinical translation of nanomedicines: Challenges, opportunities, and keys","volume":"181","author":"Younis","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"e70195","DOI":"10.1002\/mco2.70195","article-title":"Organoid-Guided Precision Medicine: From Bench to Bedside","volume":"6","author":"Tao","year":"2025","journal-title":"MedComm"},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41568-024-00756-w","article-title":"Challenging the status quo to improve the translational potential of preclinical oncology studies","volume":"25","author":"Connor","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"lnae016","DOI":"10.1093\/lifemedi\/lnae016","article-title":"Bridging the organoid translational gap: Integrating standardization and micropatterning for drug screening in clinical and pharmaceutical medicine","volume":"3","author":"Yang","year":"2024","journal-title":"Life Med."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"107533","DOI":"10.1016\/j.lungcan.2024.107533","article-title":"Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine","volume":"190","author":"Taverna","year":"2024","journal-title":"Lung Cancer"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"81","DOI":"10.2165\/11534750-000000000-00000","article-title":"Clinical pharmacokinetics of metformin","volume":"50","author":"Graham","year":"2011","journal-title":"Clin. Pharmacokinet."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.2147\/IJN.S446919","article-title":"Opportunities and challenges for inhalable nanomedicine formulations in respiratory diseases: A review","volume":"19","author":"Feng","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_304","doi-asserted-by":"crossref","unstructured":"Hong, C.-E., and Lyu, S.-Y. (2025). Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157247"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/483531a","article-title":"Raise standards for preclinical cancer research","volume":"483","author":"Begley","year":"2012","journal-title":"Nature"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"e71601","DOI":"10.7554\/eLife.71601","article-title":"Investigating the replicability of preclinical cancer biology","volume":"10","author":"Errington","year":"2021","journal-title":"elife"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1001\/jama.2019.3805","article-title":"Metformin in 2019","volume":"321","author":"Flory","year":"2019","journal-title":"JAMA"},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.cmet.2016.03.010","article-title":"Are metformin doses used in murine cancer models clinically relevant?","volume":"23","author":"Chandel","year":"2016","journal-title":"Cell Metab."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"3855","DOI":"10.1016\/j.apsb.2024.06.010","article-title":"Recent advances to address challenges in extracellular vesicle-based applications for lung cancer","volume":"14","author":"Huang","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_310","doi-asserted-by":"crossref","unstructured":"Tian, F., Chen, Z., Chen, X., and Zhao, M. (2022). Increasing trends of polypharmacy and potentially inappropriate medication use in older lung cancer patients in China: A repeated cross-sectional study. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.935764"},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Feng, Q., and Xiao, K. (2022). Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122787"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nrn3475","article-title":"Power failure: Why small sample size undermines the reliability of neuroscience","volume":"14","author":"Button","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S1470-2045(15)00027-3","article-title":"Metformin in patients with advanced pancreatic cancer: A double-blind, randomised, placebo-controlled phase 2 trial","volume":"16","author":"Kordes","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1463-1326.2004.00369.x","article-title":"Efficacy, dose\u2013response relationship and safety of once-daily extended-release metformin (Glucophage\u00ae XR) in type 2 diabetic patients with inadequate glycaemic control despite prior treatment with diet and exercise: Results from two double-blind, placebo-controlled studies","volume":"7","author":"Fujioka","year":"2005","journal-title":"Diabetes Obes. Metab."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"113895","DOI":"10.1016\/j.jconrel.2025.113895","article-title":"Peptide-based nanoassembly enhances ferroptosis in cancer to overcome paclitaxel resistance","volume":"384","author":"Lin","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"115194","DOI":"10.1016\/j.intimp.2025.115194","article-title":"Engineered nanomaterials and macrophages: Toxicity mechanisms and protective strategies","volume":"162","author":"Su","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_317","first-page":"374","article-title":"Cooperation","volume":"12","author":"McCarthy","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_318","doi-asserted-by":"crossref","unstructured":"Zhou, K., Shu, P., Zheng, H., and Li, Q. (2023). Cost-effectiveness analysis of toripalimab plus chemotherapy as the first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) without EGFR or ALK driver mutations from the Chinese perspective. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1133085"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"122537","DOI":"10.1016\/j.biomaterials.2024.122537","article-title":"\u201cOn\/off\u201d-switchable crosslinked PTX-nanoformulation with improved precise delivery for NSCLC brain metastases and restrained adverse reaction over nab-PTX","volume":"307","author":"Li","year":"2024","journal-title":"Biomaterials"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7908\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:20:35Z","timestamp":1788949235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":319,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177908"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177908","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}