{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:53:30Z","timestamp":1790744010808,"version":"4.1.0"},"reference-count":323,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine paracrine stimulation can transform TKs into oncogenic drivers, causing cancer pathogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as an attractive targeted therapy option, especially for non-small cell lung cancer (NSCLC). However, resistance to TKIs, and adverse cardiovascular effects such as heart failure, atrial fibrillation, hypertension, and sudden death, are among the most common adverse effects of TKIs. There is increasing interest in plant-derived natural products in the hunt for powerful chemosensitizer and pathway modulators for enhancing TKI activity and\/or overcoming resistance mechanisms. This highlights the mechanism of TKs\u2019 activation in cancer, the role of TKIs in NSCLC mechanisms, and the challenges posed by TKI-acquired resistance. Additionally, we explored various plant-derived natural products\u2019 bioactive compounds with the chemosensitizer and pathway-modulating potential with TKs\u2019 inhibitory and anticancer effects. Our review suggests that a combination of natural products with TKIs may provide a novel and promising strategy for overcoming resistance in lung cancer. In future, further preclinical and clinical studies are advised.<\/jats:p>","DOI":"10.3390\/cimb47070498","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T13:06:17Z","timestamp":1751288777000},"page":"498","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer"],"prefix":"10.3390","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0850-5500","authenticated-orcid":false,"given":"Faris","family":"Alrumaihi","sequence":"first","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arshad Husain","family":"Rahmani","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitrarasu Vijaya","family":"Prabhu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Microbiology and Bioinformatics, National College (Autonomous), Tiruchirapalli 620001, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3566-621X","authenticated-orcid":false,"given":"Vikalp","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Mohan College of Nursing and Paramedical Sciences, Bareilly 243302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3448-9353","authenticated-orcid":false,"given":"Shehwaz","family":"Anwar","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Mohan College of Nursing and Paramedical Sciences, Bareilly 243302, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3390\/uro4020006","article-title":"A Review on Risk Factors, Diagnostic Innovations, and Plant Based Therapies for the Management of Erectile Dysfunction","volume":"4","author":"Alrumaihi","year":"2024","journal-title":"Uro"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100966","DOI":"10.1016\/j.genrep.2020.100966","article-title":"Cinnamon and its active compounds: A potential candidate in disease and tumour management through modulating various genes activity","volume":"21","author":"Almatroodi","year":"2020","journal-title":"Gene Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Najmi, A., Javed, S.A., Al Bratty, M., and Alhazmi, H.A. (2022). Modern approaches in the discovery and development of plant-based natural products and their analogues as potential therapeutic agents. Molecules, 27.","DOI":"10.3390\/molecules27020349"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Anwar, S., Raut, R., and Alhumaydhi, F.A. (2024). A comprehensive investigation on alleviating oxidative stress and inflammation in hyperglycaemic conditions through in vitro experiments and computational analysis. Saudi J. Biol. Sci., 31.","DOI":"10.1016\/j.sjbs.2024.104003"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.2174\/1871520620666200705220307","article-title":"Natural products: Implication in cancer prevention and treatment through modulating various biological activities","volume":"20","author":"Anwar","year":"2020","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.ccell.2017.11.004","article-title":"Myeloid Cell-Derived Reactive Oxygen Species Induce Epithelial Mutagenesis","volume":"32","author":"Canli","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.trecan.2022.07.002","article-title":"Inflammation: The incubator of the tumor microenvironment","volume":"8","author":"Denk","year":"2022","journal-title":"Trends Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41467-018-05228-y","article-title":"The therapeutic significance of mutational signatures from DNA repair deficiency in cancer","volume":"9","author":"Ma","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41392-021-00648-7","article-title":"DNA damage repair: Historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/258487a0","article-title":"Control of growth of mammalian cells in cell culture","volume":"258","author":"Holley","year":"1975","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Raufi, A.G., May, M.S., Hadfield, M.J., Seyhan, A.A., and El-Deiry, W.S. (2023). Advances in Liquid Biopsy Technology and Implications for Pancreatic Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044238"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Forder, A., Zhuang, R., Souza, V.G.P., Brockley, L.J., Pewarchuk, M.E., Telkar, N., Stewart, G.L., Benard, K., Marshall, E.A., and Reis, P.P. (2023). Mechanisms Contributing to the Comorbidity of COPD and Lung Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032859"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12943-018-0801-5","article-title":"Advances in studies of tyrosine kinase inhibitors and their acquired resistance","volume":"17","author":"Jiao","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrc2559","article-title":"Targeting cancer with small molecule kinase inhibitors","volume":"9","author":"Zhang","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, W., Han, J.H., Wei, S., Yang, E.-S., Cheon, S.-Y., Bae, S.-J., Ryu, D., Chung, H.-S., and Ha, K.-T. (2024). Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor\u2013Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020807"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.21037\/atm-22-4479","article-title":"A snapshot of lung cancer: Where are we now?\u2014A narrative review","volume":"11","author":"Ibodeng","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"ref_18","unstructured":"Clark, S.B., and Alsubait, S. (2025, April 10). Non\u2013Small Cell Lung Cancer, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK562307\/."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xie, S., Wu, Z., Qi, Y., Wu, B., and Zhu, X. (2021). The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges. Biomed. Pharmacother., 138.","DOI":"10.1016\/j.biopha.2021.111450"},{"key":"ref_20","first-page":"S463","article-title":"The pivotal role of pathology in the management of lung cancer","volume":"5","author":"Davidson","year":"2013","journal-title":"J. Thorac. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"288","DOI":"10.21037\/tlcr.2016.06.07","article-title":"Non-small cell lung cancer: Current treatment and future advances","volume":"5","author":"Zappa","year":"2016","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-L\u00f3pez, S., Whiteman, Z.E., and Janes, S.M. (2021). Mapping lung squamous cell carcinoma pathogenesis through in vitro and in vivo models. Commun. Biol., 4.","DOI":"10.1038\/s42003-021-02470-x"},{"key":"ref_23","unstructured":"Sabbula, B.R., Gasalberti, D.P., Mukkamalla, S.K.R., and Anjum, F. (2025, April 10). Squamous Cell Lung Cancer, StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK564510\/."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.21037\/tcr.2020.01.40","article-title":"Clinical characteristics and treatments of large cell lung carcinoma: A retrospective study using SEER data","volume":"9","author":"Tai","year":"2020","journal-title":"Transl. Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-020-00235-0","article-title":"Small-cell lung cancer","volume":"7","author":"Rudin","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ctrv.2007.01.006","article-title":"Targeting receptor tyrosine kinase signalling in small cell lung cancer (SCLC): What have we learned so far?","volume":"33","author":"Fischer","year":"2007","journal-title":"Cancer Treat. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Cui, Y., Zheng, X., Zhao, Y., and Sun, G. (2022). Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment. Biochim. Biophys. Acta Mol. Basis Dis., 1868.","DOI":"10.1016\/j.bbadis.2022.166557"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0093-7754(01)90072-7","article-title":"Molecular genetics of small cell lung carcinoma","volume":"28","author":"Wistuba","year":"2001","journal-title":"Semin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/1758834016678149","article-title":"Current understanding and approach to well differentiated lung neuroendocrine tumors: An update on classification and management","volume":"9","author":"Hilal","year":"2017","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1001\/jamaoncol.2022.5631","article-title":"Emerging Strategies for the Treatment of Small Cell Lung Cancer: A Review","volume":"9","author":"Petty","year":"2023","journal-title":"JAMA Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12943-023-01740-y","article-title":"Lung cancer immunotherapy: Progress, pitfalls, and promises","volume":"22","author":"Lahiri","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"Joyce","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1158\/0008-5472.CAN-04-1449","article-title":"A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors","volume":"64","author":"Wyckoff","year":"2004","journal-title":"Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11523-013-0258-9","article-title":"Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC)","volume":"8","author":"Kobayashi","year":"2013","journal-title":"Target. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1111\/iwj.14075","article-title":"The use of epidermal growth factor in dermatological practice","volume":"20","author":"Shin","year":"2023","journal-title":"Int. Wound J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13045-022-01391-4","article-title":"Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance","volume":"15","author":"Fu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11523-022-00941-7","article-title":"Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases: Current Evidence and Future Perspectives on Therapeutic Strategies","volume":"18","author":"Popat","year":"2023","journal-title":"Target. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1158\/2159-8290.CD-20-1311","article-title":"Liquid Biopsy: From Discovery to Clinical Application","volume":"11","author":"Pantel","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Cicenas, J., Zalyte, E., Bairoch, A., and Gaudet, P. (2018). Kinases and Cancer. Cancers, 10.","DOI":"10.3390\/cancers10030063"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bhanumathy, K.K., Balagopal, A., Vizeacoumar, F.S., Vizeacoumar, F.J., Freywald, A., and Giambra, V. (2021). Protein Tyrosine Kinases: Their Roles and Their Targeting in Leukemia. Cancers, 13.","DOI":"10.3390\/cancers13020184"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"101","DOI":"10.7150\/ijms.1.101","article-title":"Tyrosine kinase\u2014Role and significance in Cancer","volume":"1","author":"Paul","year":"2004","journal-title":"Int. J. Med. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1146\/annurev.bi.54.070185.004341","article-title":"Protein-tyrosine kinases","volume":"54","author":"Hunter","year":"1985","journal-title":"Annu. Rev. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.37349\/en.2024.00033","article-title":"Connecting the ends: Signaling via receptor tyrosine kinases and cytoskeletal degradation in neurodegeneration","volume":"3","author":"Sengupta","year":"2024","journal-title":"Explor. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0092-8674(95)90405-0","article-title":"Protein kinases and phosphatases: The yin and yang of protein phosphorylation and signalling","volume":"80","author":"Hunter","year":"1995","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-018-0782-4","article-title":"Mechanisms of receptor tyrosine kinase activation in cancer","volume":"17","author":"Du","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0092-8674(00)00114-8","article-title":"Cell signaling by receptor tyrosine kinases","volume":"103","author":"Schlessinger","year":"2000","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cell.2010.06.011","article-title":"Cell signaling by receptor tyrosine kinases","volume":"141","author":"Lemmon","year":"2010","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0962-8924(01)02154-7","article-title":"SH2 domains, interaction modules and cellular wiring","volume":"11","author":"Pawson","year":"2001","journal-title":"Trends Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"490","DOI":"10.20892\/j.issn.2095-3941.2020.0120","article-title":"Targeting FGFR in non-small cell lung cancer: Implications from the landscape of clinically actionable aberrations of FGFR kinases","volume":"18","author":"Zhou","year":"2021","journal-title":"Cancer Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Martellucci, S., Clementi, L., Sabetta, S., Mattei, V., Botta, L., and Angelucci, A. (2020). Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far. Cancers, 12.","DOI":"10.3390\/cancers12061448"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.apsb.2015.07.001","article-title":"Mechanisms of resistance to EGFR tyrosine kinase inhibitors","volume":"5","author":"Huang","year":"2015","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3892\/or.2023.8675","article-title":"The advance of the third-generation EGFR-TKI in the treatment of non-small cell lung cancer (Review)","volume":"51","author":"Cheng","year":"2024","journal-title":"Oncol. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Zhu, X., Chen, L., Liu, L., and Niu, X. (2019). EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01044"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/acschembio.4c00028","article-title":"Chemical Scaffolds for the Clinical Development of Mutant-Selective and Reversible Fourth-Generation EGFR-TKIs in NSCLC","volume":"19","author":"Laudadio","year":"2024","journal-title":"ACS Chem. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e446","DOI":"10.1002\/mco2.446","article-title":"Receptor tyrosine kinases: Biological functions and anticancer targeted therapy","volume":"4","author":"Zhang","year":"2023","journal-title":"MedComm"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","article-title":"Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_58","first-page":"48","article-title":"Epidermal growth factor receptor (EGFR) in lung cancer: An overview and update","volume":"2","author":"Bethune","year":"2010","journal-title":"J. Thorac. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/PPO.0000000000000165","article-title":"The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia","volume":"22","author":"Pophali","year":"2016","journal-title":"Cancer J."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Xu, L., Xie, Y., Gou, Q., Cai, R., Bao, R., Huang, Y., and Tang, R. (2024). HER2-targeted therapies for HER2-positive early-stage breast cancer: Present and future. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1446414"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-024-01899-w","article-title":"Therapeutic advances of targeting receptor tyrosine kinases in cancer","volume":"9","author":"Tomuleasa","year":"2024","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1093\/jnci\/djac015","article-title":"Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer","volume":"115","author":"Wang","year":"2023","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-016-0316-8","article-title":"Serial cfDNA assessment of response and resistance to EGFR-TKI for patients with EGFR-L858R mutant lung cancer from a prospective clinical trial","volume":"9","author":"Zhou","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1056\/NEJMoa1411817","article-title":"AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer","volume":"372","author":"Yang","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1200\/JCO.2016.70.3223","article-title":"Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component","volume":"35","author":"Yang","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Christopoulos, P., Bozorgmehr, F., Br\u00fcckner, L., Chung, I., Krisam, J., Schneider, M.A., Stenzinger, A., Eickhoff, R., Mueller, D.W., and Thomas, M. (2021). Brigatinib versus other second-generation ALK inhibitors as initial treatment of anaplastic lymphoma kinase positive non-small cell lung cancer with deep phenotyping: Study protocol of the ABP trial. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08460-w"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"858","DOI":"10.20517\/cdr.2023.89","article-title":"Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma","volume":"6","author":"Sweeney","year":"2023","journal-title":"Cancer Drug Resist."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Khaddour, K., Jonna, S., Deneka, A., Patel, J.D., Abazeed, M.E., Golemis, E., Borghaei, H., and Boumber, Y. (2021). Targeting the Epidermal Growth Factor Receptor in EGFR-Mutated Lung Cancer: Current and Emerging Therapies. Cancers, 13.","DOI":"10.3390\/cancers13133164"},{"key":"ref_69","first-page":"72","article-title":"Multi-targeted tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: An era of individualized therapy","volume":"1","author":"Zhou","year":"2012","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1038\/onc.2009.198","article-title":"Activating and resistance mutations of EGFR in non-small-cell lung cancer: Role in clinical response to EGFR tyrosine kinase inhibitors","volume":"28","author":"Gazdar","year":"2009","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e000060","DOI":"10.1136\/esmoopen-2016-000060","article-title":"Mechanisms of resistance to EGFR-targeted drugs: Lung cancer","volume":"1","author":"Morgillo","year":"2016","journal-title":"ESMO Open"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12943-018-0777-1","article-title":"Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer","volume":"17","author":"Wu","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Poudel, G., Tolland, M.G., Hughes, T.P., and Pagani, I.S. (2022). Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia. Cancers, 14.","DOI":"10.3390\/cancers14143300"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.7150\/ijbs.93697","article-title":"Using Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment","volume":"20","author":"Benhar","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1021\/ml500091p","article-title":"A New Challenging and Promising Era of Tyrosine Kinase Inhibitors","volume":"5","author":"Cui","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"eaan4368","DOI":"10.1126\/science.aan4368","article-title":"The target landscape of clinical kinase drugs","volume":"358","author":"Klaeger","year":"2017","journal-title":"Science"},{"key":"ref_77","unstructured":"Codex, Y. (2025, April 10). Advancements in Targeted Kinase Inhibitors: Revolutionizing Personalized Medicine in Oncology. Yubetsu Codex Medicine & Physiology. Available online: https:\/\/codex.yubetsu.com\/article\/c020b487e78046d89a0ed3afaac73ec5."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Fukuda, S., Suda, K., Hamada, A., Oiki, H., Ohara, S., Ito, M., Soh, J., Mitsudomi, T., and Tsutani, Y. (2024). Potential Utility of a 4th-Generation EGFR-TKI and Exploration of Resistance Mechanisms-An In Vitro Study. Biomedicines, 12.","DOI":"10.20944\/preprints202406.0009.v1"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Osbourn, A., and Lanzotti, V. (2009). Introduction to the Different Classes of Natural Products. Plant-Derived Natural Products, Springer.","DOI":"10.1007\/978-0-387-85498-4"},{"key":"ref_80","first-page":"f249","article-title":"A review on utilization of ashoka plant in oxidative stress induced women reproductive health complications","volume":"11","author":"Anwar","year":"2023","journal-title":"IJCRT"},{"key":"ref_81","first-page":"261","article-title":"Prevention of non-enzymatic glycosylation (glycation): Implication in the treatment of diabetic complication","volume":"10","author":"Younus","year":"2016","journal-title":"Int. J. Health Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"6661937","DOI":"10.1155\/2021\/6661937","article-title":"6-Gingerol, a major ingredient of ginger attenuates diethylnitrosamine-induced liver injury in rats through the modulation of oxidative stress and anti-inflammatory activity","volume":"2021","author":"Alsahli","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Anwar, S., Almatroudi, A., Allemailem, K.S., Jacob Joseph, R., Khan, A.A., and Rahmani, A.H. (2020). Protective Effects of Ginger Extract against Glycation and Oxidative Stress-Induced Health Complications: An In Vitro Study. Processes, 8.","DOI":"10.3390\/pr8040468"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Alsahli, M.A., Almatroudi, A., Almogbel, M.A., Khan, A.A., Anwar, S., and Almatroodi, S.A. (2022). The Potential Role of Apigenin in Cancer Prevention and Treatment. Molecules, 27.","DOI":"10.3390\/molecules27186051"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Babiker, A.Y., and Anwar, S. (2023). Hesperidin, a Bioflavonoid in Cancer Therapy: A Review for a Mechanism of Action through the Modulation of Cell Signaling Pathways. Molecules, 28.","DOI":"10.3390\/molecules28135152"},{"key":"ref_86","first-page":"100251","article-title":"Natural products combating EGFR-TKIs resistance in cancer","volume":"13","author":"Xia","year":"2025","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_87","first-page":"447","article-title":"Challenges of conducting clinical trials of natural products to combat cancer","volume":"14","author":"Paller","year":"2016","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7988","DOI":"10.2174\/0929867328666210322103906","article-title":"Therapeutic potential of natural compounds in lung cancer","volume":"28","author":"Wilkin","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"595","DOI":"10.4103\/pm.pm_535_16","article-title":"Anti-cancer Effects of Polyphenolic Compounds in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-resistant Non-small Cell Lung Cancer","volume":"13","author":"Jeong","year":"2017","journal-title":"Pharmacogn. Mag."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/onc.2009.335","article-title":"Capsaicin causes cell-cycle arrest and apoptosis in ER-positive and -negative breast cancer cells by modulating the EGFR\/HER-2 pathway","volume":"29","author":"Thoennissen","year":"2010","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/mnfr.201000292","article-title":"Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK\/Akt, PKC\/Raf\/ERK, p38 MAPK, and AP-1 signaling","volume":"55","author":"Hwang","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.aca.2013.01.001","article-title":"Simultaneous determination of fangchinoline and tetrandrine in Stephania tetrandra S. Moore by using 1-alkyl-3-methylimidazolium-based ionic liquids as the RP-HPLC mobile phase additives","volume":"767","author":"Tang","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00280-014-2651-1","article-title":"Oxymatrine targets EGFR(p-Tyr845) and inhibits EGFR-related signaling pathways to suppress the proliferation and invasion of gastric cancer cells","volume":"75","author":"Guo","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"40800","DOI":"10.18632\/oncotarget.8315","article-title":"Tetrandrine, a Chinese plant-derived alkaloid, is a potential candidate for cancer chemotherapy","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.3892\/ijo.2014.2808","article-title":"Inhibition of IL-6\/STAT3 axis and targeting Axl and Tyro3 receptor tyrosine kinases by apigenin circumvent taxol resistance in ovarian cancer cells","volume":"46","author":"Suh","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.7150\/jca.34981","article-title":"Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro","volume":"11","author":"Huang","year":"2020","journal-title":"J. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.fct.2006.08.021","article-title":"Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis","volume":"45","author":"Leung","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_98","first-page":"1884","article-title":"Curcumin inhibits tyrosine kinase activity of p185 neu and also depletes p185 neu","volume":"5","author":"Hong","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.3892\/ijo.2015.3216","article-title":"Curcumin-induced downregulation of Axl receptor tyrosine kinase inhibits cell proliferation and circumvents chemoresistance in non-small lung cancer cells","volume":"47","author":"Kim","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"2842","DOI":"10.1111\/bph.12610","article-title":"Luteolin is effective in the non-small cell lung cancer model with L858R\/T790M EGF receptor mutation and erlotinib resistance","volume":"171","author":"Hong","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13046-020-01566-2","article-title":"Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer","volume":"39","author":"Yu","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.3892\/ol.2020.11679","article-title":"Fisetin inhibits vascular endothelial growth factor-induced angiogenesis in retinoblastoma cells","volume":"20","author":"Wang","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_103","first-page":"659","article-title":"Phase I clinical trial of the flavonoid quercetin: Pharmacokinetics and evidence for in vivo tyrosine kinase inhibition","volume":"2","author":"Ferry","year":"1996","journal-title":"Clin. Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1002\/biof.1983","article-title":"Caffeic acid phenethyl ester surmounts acquired resistance of AZD9291 in non-small cell lung cancer cells","volume":"49","author":"Twum","year":"2023","journal-title":"BioFactors"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nrc2641","article-title":"Cancer prevention by tea: Animal studies, molecular mechanisms and human relevance","volume":"9","author":"Yang","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Farabegoli, F., Govoni, M., Spisni, E., and Papi, A. (2017). EGFR inhibition by (-)-epigallocatechin-3-gallate and IIF treatments reduces breast cancer cell invasion. Biosci. Rep., 37.","DOI":"10.1042\/BSR20170168"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/mnfr.201000622","article-title":"Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases","volume":"55","author":"Shimizu","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1158\/1078-0432.CCR-09-0109","article-title":"The green tea polyphenol EGCG potentiates the antiproliferative activity of c-Met and epidermal growth factor receptor inhibitors in non-small cell lung cancer cells","volume":"15","author":"Milligan","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Minnelli, C., Cianfruglia, L., Laudadio, E., Mobbili, G., Galeazzi, R., and Armeni, T. (2021). Effect of Epigallocatechin-3-Gallate on EGFR Signaling and Migration in Non-Small Cell Lung Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111833"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s12935-019-0981-0","article-title":"(\u2212)-Epigallocatechin-3-gallate derivatives combined with cisplatin exhibit synergistic inhibitory effects on non-small-cell lung cancer cells","volume":"19","author":"Wang","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1093\/carcin\/bgi024","article-title":"Combined inhibition of PDGF and VEGF receptors by ellagic acid, a dietary-derived phenolic compound","volume":"26","author":"Labrecque","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.2174\/0929867324666170523123655","article-title":"Natural product gossypol and its derivatives in precision cancer medicine","volume":"26","author":"Zeng","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.3109\/10715762.2012.720017","article-title":"The tyrphostin AG1478 augments oridonin-induced A431 cell apoptosis by blockage of JNK MAPK and enhancement of oxidative stress","volume":"46","author":"Yu","year":"2012","journal-title":"Free Radic. Res."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1158\/1940-6207.CAPR-16-0129","article-title":"Honokiol Decreases Lung Cancer Metastasis through Inhibition of the STAT3 Signaling Pathway","volume":"10","author":"Pan","year":"2017","journal-title":"Cancer Prev. Res."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Wang, X., Liu, Q., Fu, Y., Ding, R.B., Qi, X., Zhou, X., Sun, Z., and Bao, J. (2022). Magnolol as a Potential Anticancer Agent: A Proposed Mechanistic Insight. Molecules, 27.","DOI":"10.3390\/molecules27196441"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/j.bbagen.2006.09.010","article-title":"Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation","volume":"1760","author":"Notas","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1142\/S0192415X2150035X","article-title":"20 (S)-Ginsenoside Rg3 inhibits lung cancer cell proliferation by targeting EGFR-mediated Ras\/Raf\/MEK\/ERK pathway","volume":"49","author":"Liang","year":"2021","journal-title":"Am. J. Chin. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1002\/tox.22899","article-title":"Ginsenoside Rg3 attenuates the osimertinib resistance by reducing the stemness of non-small cell lung cancer cells","volume":"35","author":"Tan","year":"2020","journal-title":"Environ. Toxicol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Liu, T., Zuo, L., Guo, D., Chai, X., Xu, J., Cui, Z., Wang, Z., and Hou, C. (2019). Ginsenoside Rg3 regulates DNA damage in non-small cell lung cancer cells by activating VRK1\/P53BP1 pathway. Biomed. Pharmacother., 120.","DOI":"10.1016\/j.biopha.2019.109483"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s13046-018-0878-0","article-title":"Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling","volume":"37","author":"Xu","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.intimp.2016.10.001","article-title":"Astragaloside IV inhibits breast cancer cell invasion by suppressing Vav3 mediated Rac1\/MAPK signaling","volume":"42","author":"Jiang","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13046-016-0388-x","article-title":"Inhibition of EZH2 via activation of SAPK\/JNK and reduction of p65 and DNMT1 as a novel mechanism in inhibition of human lung cancer cells by polyphyllin I","volume":"35","author":"Li","year":"2016","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2018.07.031","article-title":"Polyphyllin I modulates MALAT1\/STAT3 signaling to induce apoptosis in gefitinib-resistant non-small cell lung cancer","volume":"356","author":"Yang","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_124","first-page":"483","article-title":"In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism","volume":"18","author":"Jing","year":"2020","journal-title":"Chin. J. Nat. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.3892\/etm.2016.3670","article-title":"Anticancer effect of cucurbitacin B on MKN-45 cells via inhibition of the JAK2\/STAT3 signaling pathway","volume":"12","author":"Xie","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sun, C.Y., Cao, D., Ren, Q.N., Zhang, S.S., Zhou, N.N., Mai, S.J., Feng, B., and Wang, H.Y. (2021). Combination treatment with inhibitors of erk and autophagy enhances antitumor activity of betulinic acid in non\u2013small-cell lung cancer in vivo and in vitro. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.684243"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Ahmadu, A.A., Delehouz\u00e9, C., Haruna, A., Mustapha, L., Lawal, B.A., Udobre, A., Baratte, B., Triscornia, C., Autret, A., and Robert, T. (2021). Betulin, a Newly Characterized Compound in Acacia auriculiformis Bark, Is a Multi-Target Protein Kinase Inhibitor. Molecules, 26.","DOI":"10.20944\/preprints202106.0115.v1"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Jung, Y.Y., Um, J.-Y., Sethi, G., and Ahn, K.S. (2022). Potential Application of Leelamine as a Novel Regulator of Chemokine-Induced Epithelial-to-Mesenchymal Transition in Breast Cancer Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179848"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijpharm.2012.07.002","article-title":"Biopharmaceutics classification and intestinal absorption study of apigenin","volume":"436","author":"Zhang","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/ptr.1900","article-title":"Blumberg a review of the bioactivity and potential health benefits of chamomile tea (Matricaria recutita L.)","volume":"20","year":"2006","journal-title":"Phytother. Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1089\/jamp.2016.1316","article-title":"Study on the pulmonary delivery system of apigenin-loaded albumin nanocarriers with antioxidant activity","volume":"30","author":"Papay","year":"2017","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.fct.2012.12.018","article-title":"In vitro anti-inflammatory effect of apigenin in the Helicobacter pylori-infected gastric adenocarcinoma cells","volume":"53","author":"Wang","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1039\/C5FO01464F","article-title":"Apigenin ameliorates hypertension-induced cardiac hypertrophy and down-regulates cardiac hypoxia inducible factor-lalpha in rats","volume":"7","author":"Zhu","year":"2016","journal-title":"Food Funct."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Ozcelik, B., Kartal, M., and Orhan, I. (2011). Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm. Biol., 49.","DOI":"10.3109\/13880209.2010.519390"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.biopha.2018.03.111","article-title":"Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling","volume":"102","author":"Hu","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_136","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_137","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.jpba.2017.01.039","article-title":"Comparative pharmacokinetic profiles of selected irreversible tyrosine kinase inhibitors, neratinib and pelitinib, with apigenin in rat plasma by UPLC\u2013MS\/MS","volume":"137","author":"Maher","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1007\/s11030-022-10396-7","article-title":"Reckoning apigenin and kaempferol as a potential multi-targeted inhibitor of EGFR\/HER2-MEK pathway of metastatic colorectal cancer identified using rigorous computational workflow","volume":"26","author":"Sharma","year":"2022","journal-title":"Mol. Divers."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3892\/ijmm.2014.1804","article-title":"Axl receptor tyrosine kinase is a novel target of apigenin for the inhibition of cell proliferation","volume":"34","author":"Kim","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13046-018-0869-1","article-title":"Downregulating CD26\/DPPIV by apigenin modulates the interplay between Akt and Snail\/Slug signaling to restrain metastasis of lung cancer with multiple EGFR statuses","volume":"37","author":"Chang","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.febslet.2004.08.036","article-title":"Apigenin suppresses the expression of VEGF, an important factor for angiogenesis, in endothelial cells via degradation of HIF-1\u03b1 protein","volume":"575","author":"Osada","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/j.bcp.2010.02.004","article-title":"Flavonoids inhibit hypoxia-induced vascular endothelial growth factor expression by a HIF-1 independent mechanism","volume":"79","author":"Zuazo","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12964-021-00750-x","article-title":"Src family kinases, adaptor proteins and the actin cytoskeleton in epithelial-to-mesenchymal transition","volume":"19","author":"Ortiz","year":"2021","journal-title":"Cell Commun. Signal"},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Cathcart, M.C., Useckaite, Z., Drakeford, C., Semik, V., Lysaght, J., Gately, K., O\u2019Byrne, K.J., and Pidgeon, G.P. (2016). Anti-cancer effects of baicalein in non-small cell lung cancer in-vitro and in-vivo. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2740-0"},{"key":"ref_145","first-page":"2510621","article-title":"Baicalin and Baicalein Inhibit Src Tyrosine Kinase and Production of IL-6","volume":"2016","author":"Brantner","year":"2016","journal-title":"J. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Park, H.-J., Park, S.-H., Choi, Y.-H., and Chi, G.-Y. (2021). The Root Extract of Scutellaria baicalensis Induces Apoptosis in EGFR TKI-Resistant Human Lung Cancer Cells by Inactivation of STAT3. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105181"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.3892\/or.2015.4258","article-title":"Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the up regulation of miR-192-5p and suppression of PI3K\/Akt signaling pathway","volume":"34","author":"Jin","year":"2015","journal-title":"Oncol. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1007\/s11626-014-9779-5","article-title":"Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt\/\u03b2-catenin pathway","volume":"50","author":"Lu","year":"2014","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1756-9966-32-33","article-title":"MTA1 promotes the invasion and migration of non-small cell lung cancer cells by down regulating miR-125b","volume":"32","author":"Li","year":"2013","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1254\/jphs.13085FP","article-title":"Curcumin induces autophagy via activating the AMPK signaling pathway in lung adenocarcinoma cells","volume":"123","author":"Xiao","year":"2013","journal-title":"J. Pharmacol. Sci."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Lee, J., Lee, Y., Chang, G., Yu, S.L., Hsieh, W.Y., Chen, J.J., Chen, H.W., and Yang, P.C. (2011). Curcumin induces EGFR degradation in lung adenocarcinoma modulates p38 activation in intestine: The versatile adjuvant for gefitinib therapy. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023756"},{"key":"ref_152","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_153","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1002\/ptr.5056","article-title":"Coadministration of erlotinib and curcumin augmentatively reduces cell viability in lung cancer cells","volume":"28","author":"Yamauchi","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3727\/096504013X13832473330032","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."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.phymed.2012.03.005","article-title":"Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549\/DDP cell apoptosis through HIF-1\u03b1 and caspase-3 mechanisms","volume":"19","author":"Ye","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1080\/07357900802653472","article-title":"Curcumin sensitizes lung cancer cells to cisplatin-induced apoptosis through superoxide anion-mediated Bcl-2 degradation","volume":"27","author":"Chanvorachote","year":"2009","journal-title":"Cancer Investig."},{"key":"ref_157","first-page":"1","article-title":"Therapeutic potential of curcumin in human prostate cancer. II. Curcumin inhibits tyrosine kinase activity of epidermal growth factor receptor and depletes the protein [Internet]","volume":"4","author":"Dorai","year":"2000","journal-title":"Mol. Urol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/carcin\/bgi272","article-title":"Inhibition of EGFR signaling in human prostate cancer PC-3 cells by combination treatment with \u03b2-phenylethyl isothiocyanate and curcumin [Internet]","volume":"27","author":"Kim","year":"2006","journal-title":"Carcinogenesis"},{"key":"ref_159","unstructured":"(2025, June 16). A Open-label Prospective Cohort Trial of Curcumin Plus Tyrosine Kinase Inhibitors (TKI) for EGFR-Mutant Advanced NSCLC (CURCUMIN), Available online: https:\/\/clinicaltrials.gov\/study\/NCT02321293?term=Tyrosine%20Kinase%20Inhibitor&intr=Curcumin&rank=1."},{"key":"ref_160","unstructured":"(2025, June 16). Phase II Trial to Modulate Intermediate Endpoint Biomarkers in Former and Current Smokers, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03598309?intr=Curcumin%20C3%20complex%C2%AE.%20Drug:%20Lovaza%C2%AE.&rank=1."},{"key":"ref_161","unstructured":"(2025, June 16). The Thoracic Peri-Operative Integrative Surgical Care Evaluation Trial\u2014Stage III (POISE), Available online: https:\/\/clinicaltrials.gov\/study\/NCT04871412?intr=Curcumin&term=Thoracic%20Peri-Operative%20Integrative%20Surgical%20Care%20&rank=1."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"105845","DOI":"10.1016\/j.jff.2023.105845","article-title":"Flavonoids as receptor tyrosine kinase inhibitors in lung cancer","volume":"110","author":"Dev","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Almatroudi, A., Allemailem, K.S., Khan, A.A., and Almatroodi, S.A. (2022). The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment. Molecules, 27.","DOI":"10.3390\/molecules27249009"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.cbi.2019.02.020","article-title":"Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition","volume":"303","author":"Tabasum","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1186\/s40001-023-01271-8","article-title":"Biological effects and mechanisms of fisetin in cancer: A promising anti-cancer agent","volume":"28","author":"Zhou","year":"2023","journal-title":"Eur. J. Med. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e22654","DOI":"10.1096\/fj.202200669RR","article-title":"A novel 4\u2032-brominated derivative of fisetin induces cell cycle arrest and apoptosis and inhibits EGFR\/ERK1\/2\/STAT3 pathways in non-small-cell lung cancer without any adverse effects in mice","volume":"36","author":"Sabarwal","year":"2022","journal-title":"FASEB J."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Almatroudi, A., Khan, A.A., and Rahmani, A.H. (2023). Potential Therapeutic Targets of Formononetin, a Type of Methoxylated Isoflavone, and Its Role in Cancer Therapy through the Modulation of Signal Transduction Pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119719"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Tay, K.C., Tan, L.T., Chan, C.K., Hong, S.L., Chan, K.G., Yap, W.H., Pusparajah, P., Lee, L.H., and Goh, B.H. (2019). Formononetin: A Review of Its Anticancer Potentials and Mechanisms. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00820"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"48404","DOI":"10.1039\/C7RA09825A","article-title":"Synthesis, characterization and biological evaluation of formononetin derivatives as novel EGFR inhibitors via inhibiting growth, migration and inducing apoptosis in breast cancer cell line","volume":"7","author":"Lin","year":"2017","journal-title":"RSC Adv."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"31","DOI":"10.2174\/138955709787001712","article-title":"Distribution and biological activities of the flavonoid luteolin","volume":"9","year":"2009","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/sj.bjp.0702879","article-title":"Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor","volume":"128","author":"Huang","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"101740","DOI":"10.1016\/j.tice.2022.101740","article-title":"Luteolin inhibits viability, migration, angiogenesis and invasion of non-small cell lung cancer vascular endothelial cells via miR-133a-3p\/purine rich element binding protein B-mediated MAPK and PI3K\/Akt signaling pathways","volume":"75","author":"Pan","year":"2022","journal-title":"Tissue Cell"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.taap.2014.10.008","article-title":"Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways","volume":"281","author":"Pratheeshkumar","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"140392","DOI":"10.1016\/j.molstruc.2024.140392","article-title":"Investigating the role of natural flavonoids in VEGFR inhibition: Molecular modelling and biological activity in A549 lung cancer cells","volume":"1322","author":"Patel","year":"2025","journal-title":"J. Mol. Struct."},{"key":"ref_175","first-page":"4145","article-title":"Luteolin overcomes acquired resistance to osimertinib in non-small cell lung cancer cells by targeting the HGF-MET-Akt pathway","volume":"13","author":"Huang","year":"2023","journal-title":"Am. J. Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"\u00c7etinkaya, M., and Baran, Y. (2023). Therapeutic Potential of Luteolin on Cancer. Vaccines, 11.","DOI":"10.3390\/vaccines11030554"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Sakurai, M.A., Ozaki, Y., Okuzaki, D., Naito, Y., Sasakura, T., Okamoto, A., Tabara, H., Inoue, T., Hagiyama, M., and Ito, A. (2014). Gefitinib and Luteolin Cause Growth Arrest of Human Prostate Cancer PC-3 Cells via Inhibition of Cyclin G-Associated Kinase and Induction of MiR-630. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100124"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Alsahli, M.A., Almatroudi, A., Verma, A.K., Aloliqi, A., Allemailem, K.S., Khan, A.A., and Rahmani, A.H. (2021). Potential Therapeutic Targets of Quercetin, a Plant Flavonol, and Its Role in the Therapy of Various Types of Cancer through the Modulation of Various Cell Signaling Pathways. Molecules, 26.","DOI":"10.3390\/molecules26051315"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuro.2020.03.002","article-title":"Mechanistic exploration of quercetin against metronidazole induced neurotoxicity in rats: Possible role of nitric oxide isoforms and inflammatory cytokines","volume":"79","author":"Chaturvedi","year":"2020","journal-title":"Neurotoxicology"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Li, Y., Yao, J., Han, C., Yang, J., Chaudhry, M.T., Wang, S., Liu, H., and Yin, Y. (2016). Quercetin, Inflammation and Immunity. Nutrients, 8.","DOI":"10.3390\/nu8030167"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Tang, S.-M., Deng, X.-T., Zhou, J., Li, Q.-P., Ge, X.-X., and Miao, L. (2020). Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed. Pharm. Ther., 121.","DOI":"10.1016\/j.biopha.2019.109604"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1080\/01635581.2021.1957487","article-title":"Quercetin inhibits the epithelial to mesenchymal transition through suppressing Akt mediated nuclear translocation of \u03b2-catenin in lung cancer cell line","volume":"74","author":"Elumalai","year":"2022","journal-title":"Nutr. Cancer"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2928","DOI":"10.1080\/14786419.2017.1385015","article-title":"Interactions of quercetin with receptor tyrosine kinases associated with human lung carcinoma","volume":"32","author":"Baby","year":"2018","journal-title":"Nat. Product Res."},{"key":"ref_184","first-page":"30","article-title":"Anti-angiogenesis property by Quercetin compound targeting VEGFR2 elucidated in a computational approach","volume":"2","author":"Basha","year":"2014","journal-title":"Eur. J. Biotechnol. Biosci."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1089\/ars.2009.2816","article-title":"Flavonoids as protein kinase inhibitors for cancer chemoprevention on: Direct binding and molecular modeling","volume":"13","author":"Hou","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/S1097-2765(05)00089-4","article-title":"Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine","volume":"6","author":"Walker","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1111\/j.1476-5381.2009.00440.x","article-title":"Differential effects of quercetin, apigenin and genistein on signaling pathways of protease-activated receptors PAR1 and PAR4 in platelets","volume":"158","author":"Rivera","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_188","first-page":"856","article-title":"Quercetin and its role in biological functions: An updated review","volume":"17","author":"Kim","year":"2018","journal-title":"EXCLI J."},{"key":"ref_189","doi-asserted-by":"crossref","unstructured":"Esp\u00edndola, K.M.M., Ferreira, R.G., Narvaez, L.E.M., Silva Rosario, A.C.R., da Silva, A.H.M., Silva, A.G.B., Vieira, A.P.O., and Monteiro, M.C. (2019). Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00541"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"105759","DOI":"10.1016\/j.phrs.2021.105759","article-title":"Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer","volume":"171","author":"Mirzaei","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Ning, X., Ren, X., Xie, X., Yan, P., Wang, D., and Huang, X. (2020). A caffeic acid phenethyl ester analog inhibits the proliferation of nasopharyngeal carcinoma cells via targeting epidermal growth factor receptor. J. Biochem. Mol. Toxicol., 34.","DOI":"10.1002\/jbt.22491"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.21873\/anticanres.17317","article-title":"Combined Treatment of Caffeic Acid Phenethyl Ester with Docetaxel Inhibits Survival of Non-small-cell Lung Cancer Cells via Suppression of c-MYC","volume":"44","author":"Kuo","year":"2024","journal-title":"Anticancer Res."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Almatroodi, S.A., Almatroudi, A., Khan, A.A., Alhumaydhi, F.A., Alsahli, M.A., and Rahmani, A.H. (2020). Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer. Molecules, 25.","DOI":"10.3390\/molecules25143146"},{"key":"ref_194","first-page":"16","article-title":"Anticancer effects and molecular mechanisms of epigallocatechin-3-gallate. Integr","volume":"3","author":"Min","year":"2014","journal-title":"Med. Res."},{"key":"ref_195","first-page":"1907","article-title":"Preparation of catechin extracts and nanoemulsions from green tea leaf waste and their inhibition effect on prostate cancer cell PC-3","volume":"11","author":"Tsai","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_196","first-page":"5059","article-title":"Inhibition of lung cancer cells A549 and H460 by curcuminoid extracts and nanoemulsions prepared from Curcuma Longa Linnaeus","volume":"10","author":"Chang","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.bbrc.2007.06.030","article-title":"The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells","volume":"360","author":"Sadava","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Rahmani, A.H., Al Shabrmi, F.M., Allemailem, K.S., Aly, S.M., and Khan, M.A. (2015). Implications of green tea and its constituents in the prevention of cancer via the modulation of cell signaling pathway. Biomed. Res. Int., 2015.","DOI":"10.1155\/2015\/925640"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.1038\/s41598-020-62136-2","article-title":"Anticancer effects of epigallocatechin-3-gallate nanoemulsion on lung cancer cells through the activation of AMP-activated protein kinase signaling pathway","volume":"10","author":"Chen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ijc.21809","article-title":"Green tea polyphenol stimulates cancer preventive effects of celecoxib in human lung cancer cells by upregulation of GADD153 gene","volume":"119","author":"Suganuma","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1002\/ijc.23585","article-title":"Synergistic inhibition of head and neck tumor growth by green tea (\u2212)-epigallocatechin-3-gallate and EGFR tyrosine kinase inhibitor","volume":"123","author":"Zhang","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_202","first-page":"1","article-title":"Antiglycating potential of ellagic acid against glucose and methylglyoxal induced glycation of superoxide dismutase","volume":"8","author":"Anwar","year":"2017","journal-title":"J. Protein Proteom."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1111\/1759-7714.13487","article-title":"Combination effects of ellagic acid with erlotinib in a Ba\/F3 cell line expressing EGFR H773_V774 insH mutation","volume":"11","author":"Xie","year":"2020","journal-title":"Thorac. Cancer"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s13020-023-00869-8","article-title":"The potential roles of gossypol as anticancer agent: Advances and future directions","volume":"18","author":"Paunovic","year":"2023","journal-title":"Chin. Med."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Pal, D., Sahu, P., Sethi, G., Wallace, C.E., and Bishayee, A. (2022). Gossypol and its natural derivatives: Multitargeted phytochemicals as potential drug candidates for oncologic diseases. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122624"},{"key":"ref_206","doi-asserted-by":"crossref","unstructured":"Xu, J., Zhu, G.Y., Cao, D., Pan, H., and Li, Y.W. (2019). Gossypol overcomes EGFR-TKIs resistance in non-small cell lung cancer cells by targeting YAP\/TAZ and EGFRL858R\/T790M. Biomed. Pharmacother., 115.","DOI":"10.1016\/j.biopha.2019.108860"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Wang, Y., Lai, H., Fan, X., Luo, L., Duan, F., Jiang, Z., Wang, Q., Leung, E.L., Liu, L., and Yao, X. (2018). Gossypol inhibits non-small cell lung cancer cells proliferation by targeting EGFRL858R\/T790M. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00728"},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Ranaware, A.M., Banik, K., Deshpande, V., Padmavathi, G., Roy, N.K., Sethi, G., Fan, L., Kumar, A.P., and Kunnumakkara, A.B. (2018). Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082362"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"5277","DOI":"10.2174\/1381612821666150928155612","article-title":"Reviewing the role of resveratrol as a natural modulator of microglial activities","volume":"21","author":"Porro","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Salehi, B., Mishra, A.P., Nigam, M., Sener, B., Kilic, M., Sharifi-Rad, M., Fokou, P.V.T., Martins, N., and Sharifi-Rad, J. (2018). Resveratrol: A Double-Edged sword in health benefits. Biomedicines, 6.","DOI":"10.3390\/biomedicines6030091"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.bcp.2010.06.027","article-title":"Resveratrol, a dietary polyphenolic phytoalexin, is a functional scavenger of peroxynitrite","volume":"80","author":"Holthoff","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2174\/157018012798192928","article-title":"Antioxidant activity of Resveratrol Analogs","volume":"9","author":"Calil","year":"2012","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"542937","DOI":"10.1100\/2012\/542937","article-title":"PHBV\/PCL Micro particles for Controlled Release of Resveratrol: Physicochemical characterization, antioxidant potential, and effect on hemolysis of human erythrocytes","volume":"2012","author":"Mendes","year":"2012","journal-title":"Sci. World J."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1467-2494.2000.00019.x","article-title":"Resveratrol: An original mechanism on tyrosinase inhibition","volume":"22","author":"Bernard","year":"2000","journal-title":"Int. J. Cosmet. Sci."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"16340","DOI":"10.1074\/jbc.M200678200","article-title":"Oxyresveratrol and Hydroxystilbene Compounds: Inhibitory effect on tyrosinase and mechanism of action","volume":"277","author":"Kim","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Zhu, Y., He, W., Gao, X., Li, B., Mei, C., Xu, R., and Chen, H. (2015). Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9\/G NSCLC cells. Sci. Rep., 5.","DOI":"10.1038\/srep17730"},{"key":"ref_217","first-page":"259","article-title":"Cancer prevention and therapeutics: Panax ginseng","volume":"9","author":"Helms","year":"2004","journal-title":"Altern. Med. Rev."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/ptr.2786","article-title":"Ember Chemo preventive effect of Panax ginseng","volume":"23","author":"Varjas","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Zheng, M., Xin, Y., Li, Y., Xu, F., Xi, X., Guo, H., Cui, X., Cao, H., Zhang, X., and Han, C. (2018). Ginsenosides: A potential neuroprotective agent. BioMed Res. Int., 2018.","DOI":"10.1155\/2018\/8174345"},{"key":"ref_220","first-page":"953","article-title":"Ginsenoside Rg3 promotes the antitumor activity of gefitinib in lung cancer cell lines","volume":"17","author":"Dai","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrm757","article-title":"The snail superfamily of zinc-finger transcription factors","volume":"3","author":"Nieto","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/crj.12976","article-title":"CD146-mediated acquisition of stemness phenotype enhances tumour invasion metastasis after EGFR-TKI resistance in lung cancer","volume":"13","author":"Zhang","year":"2019","journal-title":"Clin. Respir. J."},{"key":"ref_223","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_224","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1097\/CAD.0000000000000781","article-title":"Ginsenoside Rd reverses cisplatin resistance in non-small-cell lung cancer A549 cells by downregulating the nuclear factor erythroid 2-related factor 2 pathway","volume":"30","author":"Chian","year":"2019","journal-title":"Anticancer. Drugs"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.biopha.2017.09.129","article-title":"Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by down regulating PD-L1 and resuming immune","volume":"96","author":"Jiang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"119414","DOI":"10.1016\/j.lfs.2021.119414","article-title":"Astragaloside IV-targeting miRNA-1 attenuates lipopolysaccharide-induced cardiac dysfunction in rats through inhibition of apoptosis and autophagy","volume":"275","author":"Wang","year":"2021","journal-title":"Life Sci."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.2147\/DMSO.S304817","article-title":"Astragaloside IV alleviates liver inflammation, oxidative stress and apoptosis to protect against experimental non-alcoholic fatty liver disease","volume":"14","author":"Liang","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"119068","DOI":"10.1016\/j.lfs.2021.119068","article-title":"Astragaloside IV protects against podocyte apoptosis by inhibiting oxidative stress via activating PPAR\u03b3 Klotho-FoxO1 axis in diabetic nephropathy","volume":"269","author":"Xing","year":"2021","journal-title":"Life Sci."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ddr.21878","article-title":"Astragaloside IV enhances the sensibility of lung adenocarcinoma cells to bevacizumab by inhibiting autophagy","volume":"83","author":"Li","year":"2021","journal-title":"Drug Dev. Res."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1159\/000482025","article-title":"Astragaloside IV induced miR-134 expression reduces EMT and increases chemotherapeutic sensitivity by suppressing CREB1 signaling in colorectal cancer cell line SW-480","volume":"43","author":"Ye","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_231","first-page":"1551","article-title":"Astragaloside IV inhibits the progression of liver cancer by modulating macrophage polarization through the TLR4\/NF-\u03baB\/STAT3 signaling pathway","volume":"14","author":"Min","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1002\/jcp.27196","article-title":"Astragaloside IV enhances taxol chemo sensitivity of breast cancer via caveolin-1-targeting oxidant damage","volume":"234","author":"Zheng","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_233","doi-asserted-by":"crossref","unstructured":"Dai, P., Liu, D., Zhang, L., Ye, J., Wang, Q., Zhang, H.W., Lin, X.H., and Lai, G.X. (Tumor. Biol., 2017). Astragaloside IV sensitizes non-small cell lung cancer cells to gefitinib potentially via regulation of SIRT6, Tumor. Biol., ahead of print.","DOI":"10.1177\/1010428317697555"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"175449","DOI":"10.1016\/j.ejphar.2022.175449","article-title":"Research progress on the antitumor effects of astragaloside IV","volume":"938","author":"Zhou","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Tian, Y., Gong, G.Y., Ma, L.L., Wang, Z.Q., Song, D., and Fang, M.Y. (2020). Anti-cancer effects of Polyphyllin I: An update in 5 years. Chem. Biol. Interact., 316.","DOI":"10.1016\/j.cbi.2019.108936"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1248\/bpb.b17-00271","article-title":"Polyphyllin I Overcomes EMT-Associated Resistance to Erlotinib in Lung Cancer Cells via IL-6\/STAT3 Pathway Inhibition","volume":"40","author":"Lou","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"376","DOI":"10.2174\/1568009616666161213141608","article-title":"Polyphyllin II Restores Sensitization of the Resistance of PC-9\/ZD Cells to Gefitinib by a Negative Regulation of the PI3K\/Akt\/mTOR Signaling Pathway","volume":"17","author":"Zheng","year":"2017","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_238","first-page":"77","article-title":"Cucurbitacin\u2014A promising target for cancer therapy","volume":"7","author":"Alghasham","year":"2013","journal-title":"Int. J. Health Sci."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1021\/np049883o","article-title":"Cucurbitane triterpenoids from Leucopaxillus gentianeus","volume":"67","author":"Clericuzio","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1039\/b418841c","article-title":"Cucurbitacins and cucurbitane glycosides: Structures and biological activities","volume":"22","author":"Chen","year":"2005","journal-title":"Nat. Prod. Rep."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.canlet.2012.01.033","article-title":"The definition and significance of Cucurbitacin B a STAT3 inhibitors","volume":"328","author":"Wiart","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1021\/np060213n","article-title":"Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of Leucopaxillus gentianeus","volume":"69","author":"Clericuzio","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jphotobiol.2009.03.005","article-title":"Interaction of cucurbitacins with human serum albumin: Thermodynamic characteristics influence on the binding of site specific ligands","volume":"95","author":"Jraij","year":"2009","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1111\/j.1349-7006.2008.00899.x","article-title":"Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo","volume":"99","author":"Wakimoto","year":"2008","journal-title":"Cancer Sci."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.canlet.2013.01.008","article-title":"Cucurbitacin B potently suppresses non-small-cell lung cancer growth: Identification of intracellular thiols as critical targets","volume":"332","author":"Kausar","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_246","first-page":"957","article-title":"Not all mutations of KRAS predict poor prognosis in patients with colorectal cancer","volume":"12","author":"Li","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/cgt.2014.18","article-title":"Knockdown of cancerous inhibitor of protein phosphatase 2A may sensitize NSCLC cells to cisplatin","volume":"21","author":"Wei","year":"2014","journal-title":"Cancer Gene Ther."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.cell.2007.03.047","article-title":"The tumor suppressor PP2A Abeta regulates the RalA GTPase","volume":"129","author":"Sablina","year":"2007","journal-title":"Cell"},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Liu, P., Xiang, Y., Liu, X., Zhang, T., Yang, R., Chen, S., Xu, L., Yu, Q., Zhao, H., and Zhang, L. (2019). Cucurbitacin B induces the lysosomal degradation of EGFR and suppresses the CIP2A\/PP2A\/Akt signaling axis in gefitinib-resistant non-small cell lung cancer. Molecules, 24.","DOI":"10.3390\/molecules24030647"},{"key":"ref_250","doi-asserted-by":"crossref","unstructured":"Hong, S.H., Ku, J.M., Lim, Y.S., Lee, S.Y., Kim, J.H., Cheon, C., and Ko, S.G. (2020). Cucurbitacin D overcomes gefitinib resistance by blocking EGF binding to EGFR and inducing cell death in NSCLCs. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00062"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13570","article-title":"Therapeutic applications of betulinic acid nanoformulation","volume":"1421","author":"Saneja","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_252","first-page":"8781690","article-title":"Betulinic acid suppresses breast cancer metastasis by targeting GRP78-mediated glycolysis and ER stress apoptotic pathway Oxid","volume":"2019","author":"Zheng","year":"2019","journal-title":"Med. Cell Longev."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1158\/1535-7163.MCT-12-0026","article-title":"Safe Betulinic acid targets YY1 and ErbB2 through cannabinoid receptor-dependent disruption of microRNA-27a: ZBTB10 in breast cancer Mol","volume":"11","author":"XLiu","year":"2012","journal-title":"Cancer Ther."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/s41419-018-0669-8","article-title":"Betulinic acid chemosensitizes breast cancer by triggering ER stress-mediated apoptosis by directly targeting GRP78","volume":"9","author":"Cai","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3390\/molecules14062016","article-title":"Pentacyclic triterpene distribution in various plants\u2014Rich sources for a new group of multi-potent plant extracts","volume":"14","author":"Trojan","year":"2009","journal-title":"Molecules"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/med.10053","article-title":"Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection","volume":"24","author":"Cichewicz","year":"2004","journal-title":"Med. Res. Rev."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.3390\/molecules13102482","article-title":"Variation of ursolic acid content in eight Ocimum species from northeastern Brazil","volume":"13","author":"Silva","year":"2008","journal-title":"Molecules"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-2007-967106","article-title":"Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L.","volume":"73","author":"Winkler","year":"2007","journal-title":"Planta Med."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1055\/s-2006-951723","article-title":"Physical, chemical and pharmacological characterization of a new oleo gel-forming triterpene extract from the outer bark of birch (betulae cortex)","volume":"72","author":"Laszczyk","year":"2006","journal-title":"Planta Med."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1039\/C6GC02641A","article-title":"Toward a benign strategy for the manufacturing of betulinic acid","volume":"19","author":"Ressmann","year":"2017","journal-title":"Green Chem."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.foodchem.2012.07.088","article-title":"A novel one-step microbial transformation of betulin to betulinic acid catalysed by Cunninghamella blakesleeana","volume":"136","author":"Feng","year":"2013","journal-title":"Food Chem."},{"key":"ref_262","doi-asserted-by":"crossref","unstructured":"Madsen, K.M., Udatha, G.D., Semba, S., Otero, J.M., Koetter, P., Nielsen, J., Ebizuka, Y., Kushiro, T., and Panagiotou, G. (2011). Linking genotype and phenotype of Saccharomyces cerevisiae strains reveals metabolic engineering targets and leads to triterpene hyper-producers. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0014763"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-arplant-050312-120229","article-title":"Triterpene biosynthesis in plants","volume":"65","author":"Thimmappa","year":"2014","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.3892\/mmr.2016.5792","article-title":"Betulinic acid and the pharmacological effects of tumour suppression","volume":"14","author":"Zhang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"4481","DOI":"10.1111\/bph.13233","article-title":"Betulinic acid exerts anti-hepatitis C virus activity via the suppression of NF-\u03baB and MAPK-ERK1\/2-mediated COX-2 expression","volume":"172","author":"Lin","year":"2015","journal-title":"Br. J. Pharm."},{"key":"ref_266","first-page":"113","article-title":"Pharmacological properties of the ubiquitous natural product botuli Eur","volume":"29","author":"Alakurtti","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.cyto.2014.09.004","article-title":"Betulinic acid attenuates lung injury by modulation of inflammatory cytokine response in experimentally-induced polymicrobial sepsis in mice","volume":"71","author":"Lingaraju","year":"2015","journal-title":"Cytokine"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/tox.22621","article-title":"Effects and mechanisms of betulinic acid on improving EGFR TKI-resistance of lung cancer cells","volume":"33","author":"Ko","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/JTO.0000000000000033","article-title":"A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)","volume":"9","author":"Shi","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_270","first-page":"98","article-title":"Betulinic acid inhibits stemness and EMT of pancreatic cancer cells via activation of AMPK signaling","volume":"54","author":"Sun","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"111664","DOI":"10.1016\/j.ejmech.2019.111664","article-title":"Natural products as important tyrosine kinase inhibitors","volume":"182","author":"Yin","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"28260","DOI":"10.18632\/oncotarget.16002","article-title":"Identifying the structure-activity relationship of leelamine necessary for inhibiting intracellular cholesterol transport","volume":"8","author":"Gowda","year":"2017","journal-title":"Oncotarget"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"563","DOI":"10.5483\/BMBRep.2021.54.11.101","article-title":"Drug evaluation based on phosphomimetic PDHA1 reveals the complexity of activity-related cell death in A549 non-small cell lung cancer cells","volume":"54","author":"Jin","year":"2021","journal-title":"BMB Rep."},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Wu, J., Li, Y., He, Q., and Yang, X. (2023). Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment. Molecules, 28.","DOI":"10.3390\/molecules28031022"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"204","DOI":"10.7150\/ijbs.22955","article-title":"Combination Strategies Using EGFR-TKi in NSCLC Therapy: Learning from the Gap between Pre-Clinical Results and Clinical Outcomes","volume":"14","author":"Yang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"e00149","DOI":"10.1002\/prp2.149","article-title":"Analysis of Drug Combinations: Current Methodological Landscape","volume":"3","author":"Foucquier","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_277","doi-asserted-by":"crossref","unstructured":"Zhong, W., Qin, Y., Chen, S., and Sun, T. (2017). Antitumor Effect of Natural Product Molecules against Lung Cancer. A Global Scientific Vision-Prevention, Diagnosis, and Treatment of Lung Cancer, InTech.","DOI":"10.5772\/67241"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"38022","DOI":"10.18632\/oncotarget.16723","article-title":"Combination therapy in combating cancer","volume":"8","author":"Homayouni","year":"2017","journal-title":"Oncotarget"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"e09519","DOI":"10.1016\/j.heliyon.2022.e09519","article-title":"Synergistic effects of natural compounds and conventional chemotherapeutic agents: Recent insights for the development of cancer treatment strategies","volume":"8","author":"Uribe","year":"2022","journal-title":"Heliyon"},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Bo\u021ba, M., Vlaia, L., J\u00eejie, A.-R., Marcovici, I., Cri\u015fan, F., Oancea, C., Dehelean, C.A., Mateescu, T., and Moac\u0103, E.-A. (2024). Exploring Synergistic Interactions between Natural Compounds and Conventional Chemotherapeutic Drugs in Preclinical Models of Lung Cancer. Pharmaceuticals, 17.","DOI":"10.3390\/ph17050598"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s43094-023-00465-5","article-title":"Anticancer Plant-Derivatives: Deciphering Their Oncopreventive and Therapeutic Potential in Molecular Terms","volume":"9","author":"Gahtori","year":"2023","journal-title":"Future J. Pharm. Sci."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"112075","DOI":"10.1016\/j.jep.2019.112075","article-title":"The Concurrent Treatment of Scutellaria baicalensis Georgi Enhances the Therapeutic Efficacy of Cisplatin but Also Attenuates Chemotherapy-Induced Cachexia and Acute Kidney Injury","volume":"243","author":"Huang","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.lungcan.2011.06.001","article-title":"Marsdenia Tenacissima Extract Restored Gefitinib Sensitivity in Resistant Non-Small Cell Lung Cancer Cells","volume":"75","author":"Han","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_284","first-page":"109","article-title":"Sulforaphane reverses gefitinib tolerance in human lung cancer cells via modulation of sonic hedgehog signaling","volume":"15","author":"Wang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_285","doi-asserted-by":"crossref","unstructured":"Han, Y., Shi, J., Xu, Z., Zhang, Y., Cao, X., Yu, J., Li, J., and Xu, S. (2022). Identification of solamargine as a cisplatin sensitizer through phenotypical screening in cisplatin-resistant NSCLC organoids. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.802168"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41419-020-02880-5","article-title":"Hederagenin potentiated cisplatin and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells","volume":"11","author":"Wang","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/j.ijbiomac.2022.11.123","article-title":"Molecular mechanism of ion channel protein TMEM16A regulated by natural product of narirutin for lung cancer adjuvant treatment","volume":"223","author":"Shi","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.phymed.2018.04.058","article-title":"Curcumin enhances cisplatin sensitivity of human NSCLC cell lines through influencing Cu-Sp1-CTR1 regulatory loop","volume":"48","author":"Zhang","year":"2018","journal-title":"Phytomedicine"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"9725","DOI":"10.1021\/jm4014168","article-title":"Targeted polysaccharide nanoparticle for adamplatin prodrug delivery","volume":"56","author":"Yang","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.3748\/wjg.14.1491","article-title":"Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents: Doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells","volume":"14","author":"Pinmai","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1007\/s12010-018-2869-1","article-title":"Synergistic Anticancer Effect of a Combination of Paclitaxel and 5-Demethylnobiletin Against Lung Cancer Cell Line In Vitro and In Vivo","volume":"187","author":"Tan","year":"2019","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_292","doi-asserted-by":"crossref","unstructured":"Peng, M., Zheng, Z., Chen, S., Fang, L., Feng, R., Zhang, L., Tang, Q., and Liu, X. (2022). Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial-Mesenchymal Transition by Aloe-Emodin Via PI3K\/Akt\/TWIS1 Signal Blockage. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.908031"},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Jiao, L., Xu, J., Sun, J., Chen, Z., Gong, Y., Bi, L., Lu, Y., Yao, J., Zhu, W., and Hou, A. (2019). Chinese Herbal Medicine Combined With EGFR-TKI in EGFR Mutation-Positive Advanced Pulmonary Adenocarcinoma (CATLA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.00732"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/cyto.a.23869","article-title":"Yiqi Chutan Tang Reduces Gefitinib-Induced Drug Resistance in Non-Small-Cell Lung Cancer by Targeting Apoptosis and Autophagy","volume":"97","author":"Zhang","year":"2020","journal-title":"Cytom. A"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1007\/s10616-017-0124-1","article-title":"Synergistic tumor suppression by a Perilla frutescens-derived methoxyflavanone and anti-cancer tyrosine kinase inhibitors in A549 human lung adenocarcinoma","volume":"70","author":"Fujimura","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_296","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_297","doi-asserted-by":"crossref","first-page":"102824","DOI":"10.1016\/j.ctrv.2024.102824","article-title":"Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development","volume":"130","author":"Corvaja","year":"2024","journal-title":"Cancer Treat. Rev."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"9662","DOI":"10.1021\/acs.jmedchem.2c00704","article-title":"Discovery of BLU-945, a Reversible, Potent, and Wild-Type-Sparing Next-Generation EGFR Mutant Inhibitor for Treatment-Resistant Non-Small-Cell Lung Cancer","volume":"65","author":"Eno","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.21037\/tcr-24-406","article-title":"Fourth-generation epidermal growth factor receptor-tyrosine kinases inhibitors: Hope and challenges","volume":"13","author":"Su","year":"2024","journal-title":"Transl. Cancer Res."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41571-020-0341-y","article-title":"Targeting apoptosis in cancer therapy","volume":"17","author":"Carneiro","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"205","DOI":"10.15171\/apb.2019.024","article-title":"Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics","volume":"9","author":"Jan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"11203","DOI":"10.1158\/0008-5472.CAN-05-1965","article-title":"A novel dietary triterpene Lupeol induces fas-mediated apoptotic death of androgen-sensitive prostate cancer cells and inhibits tumor growth in a xenograft model","volume":"65","author":"Saleem","year":"2005","journal-title":"Cancer Res."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1038\/cdd.2011.30","article-title":"Caspases and cancer","volume":"18","author":"Olsson","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1097\/IGC.0b013e31820d3e42","article-title":"Changes in activities of caspase-8 and caspase-9 in human cervical malignancy","volume":"21","author":"Ekonomopoulou","year":"2011","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1093\/carcin\/23.1.143","article-title":"Curcumin (diferuloylmethane) induces apoptosis through activation of caspase-8, BID cleavage and cytochrome c release: Its suppression by ectopic expression of Bcl-2 and Bcl-xl","volume":"23","author":"Anto","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.foodchem.2014.07.005","article-title":"White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage","volume":"169","author":"Hajiaghaalipour","year":"2015","journal-title":"Food Chem."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1039\/c1fo10030k","article-title":"Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cells","volume":"2","author":"Kim","year":"2011","journal-title":"Food Funct."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1142\/S0192415X13500961","article-title":"Hispolon from Phellinus linteus induces G0\/G1 cell cycle arrest and apoptosis in NB4 human leukaemia cells","volume":"41","author":"Chen","year":"2013","journal-title":"Am. J. Chin. Med."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"105871","DOI":"10.1016\/j.fitote.2024.105871","article-title":"Comparative analysis of chemical profiles, antioxidant, antibacterial, and anticancer effects of essential oils of two Thymus species from Montenegro","volume":"174","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1142\/S0192415X24500241","article-title":"Curcumin analog L48H37 induces apoptosis in human Oral cancer cells by activating caspase cascades and downregulating the inhibitor of apoptosis proteins through JNK\/p38 signaling","volume":"52","author":"Su","year":"2024","journal-title":"Am. J. Chin. Med."},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Auwal, A., Al Banna, M.H., Pronoy, T.U., Hossain, M.M., Rashel, K.M., Kabir, S.R., Ansary, M.R., and Islam, F. (Anti-Cancer Agents Med. Chem., 2025). In vitro and In vivo Growth Inhibition and apoptosis of cancer cells by ethyl 4-[(4-methylbenzyl) oxy] benzoate complex, Anti-Cancer Agents Med. Chem., ahead of print.","DOI":"10.2174\/0118715206359811241227032311"},{"key":"ref_312","doi-asserted-by":"crossref","unstructured":"Huang, S.T., Huang, C.C., Huang, W.L., Lin, T.K., Liao, P.L., Wang, P.W., Liou, C.W., and Chuang, J.H. (2017). Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction. Sci. Rep., 7.","DOI":"10.1038\/srep40382"},{"key":"ref_313","doi-asserted-by":"crossref","unstructured":"Yan, N., Guo, S., Zhang, H., Zhang, Z., Shen, S., and Li, X. (2022). BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.863043"},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.ccell.2015.08.001","article-title":"BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms That Determine Their Sensitivity to Pharmacologic Inhibition","volume":"28","author":"Yao","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nature23291","article-title":"Tumours with Class 3 BRAF Mutants are Sensitive to the Inhibition of Activated RAS","volume":"548","author":"Yao","year":"2017","journal-title":"Nature"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1038\/s41388-018-0171-x","article-title":"Classifying BRAF Alterations in Cancer: New Rational Therapeutic Strategies for Actionable Mutations","volume":"37","author":"Dankner","year":"2018","journal-title":"Oncogene"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1200\/JCO.2010.33.1280","article-title":"Clinical Characteristics of Patients with Lung Adenocarcinomas Harboring BRAF Mutations","volume":"29","author":"Paik","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1097\/JTO.0000000000000344","article-title":"Clinical Characteristics and Course of 63 Patients with BRAF Mutant Lung Cancers","volume":"9","author":"Litvak","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_319","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive Molecular Profiling of Lung Adenocarcinoma. Nature, 511, 543\u2013550.","DOI":"10.1038\/nature13385"},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3390\/receptors3010005","article-title":"Role and Function of Receptor Tyrosine Kinases in BRAF Mutant Cancers","volume":"3","author":"Biersack","year":"2024","journal-title":"Receptors"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/2159-8290.CD-11-0341","article-title":"EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib","volume":"2","author":"Corcoran","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1158\/2159-8290.CD-12-0408","article-title":"Genotype-selective combination therapies for melanoma identified by high-throughput drug screening","volume":"3","author":"Held","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_323","doi-asserted-by":"crossref","unstructured":"Baur, F., Nietzer, S.L., Kunz, M., Saal, F., Jeromin, J., Matschos, S., Linnebacher, M., Walles, H., Dandekar, T., and Dandekar, G. (2020). Connecting cancer pathways to tumor engines: A stratification tool for colorectal cancer combining human in vitro tissue models with Boolean in silico models. Cancers, 12.","DOI":"10.3390\/cancers12010028"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/498\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:01:48Z","timestamp":1760032908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":323,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cimb47070498"],"URL":"https:\/\/doi.org\/10.3390\/cimb47070498","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}