{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:17:41Z","timestamp":1793625461365,"version":"4.5.0"},"reference-count":177,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:00:00Z","timestamp":1772928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Imperatorin, a naturally occurring furanocoumarin found in several medicinal plants, has attracted considerable scientific interest due to its broad spectrum of pharmacological activities and emerging relevance in oncology. In recent years, an increasing number of experimental studies have investigated its biological effects and molecular mechanisms across different tumor models. Due to this, the review synthesizes the current preclinical and pharmacological evidence on imperatorin in cancer, with the aim of consolidating the main mechanistic pathways involved in its antitumor activity, identifying its therapeutic opportunities, and highlighting existing challenges and future research perspectives. Available in vitro and in vivo studies demonstrate that imperatorin exerts multi-targeted antitumor effects, including the induction of apoptosis, inhibition of proliferation, suppression of angiogenesis, modulation of oxidative stress, attenuation of inflammation, and disruption of oncogenic signaling pathways such as PI3K\/Akt, MAPK, mTOR, and NF-\u03baB. Imperatorin also influences the tumor microenvironment by reducing pro-inflammatory mediators, impairing stromal\u2013tumor cross-talk, and enhancing immune-cell-mediated cytotoxicity. In addition, we also summarize pharmacokinetic and safety limitations that hinder clinical translation, including low oral bioavailability, extensive plasma protein binding, cytochrome P450 interactions, and insufficient toxicological data. In parallel, we highlight recent advances in the genetics and biosynthesis of imperatorin, which support perspectives for sustainable production and structural optimization of imperatorin derivatives. Finally, we outline key knowledge gaps and future directions, including improved delivery strategies, investigation of additional regulatory pathways, and more robust in vivo and translational studies, emphasizing that imperatorin remains a promising yet still incompletely characterized anticancer candidate. The review highlights the need for more comprehensive pharmacokinetic and safety assessments, as well as the development of improved delivery systems to address absorption and stability challenges. Further research into imperatorin\u2019s effects on autophagy, ferroptosis, metabolic reprogramming, and the immune microenvironment is essential to deepen mechanistic understanding. Additionally, fully elucidating the biosynthetic enzymes responsible for imperatorin formation may facilitate sustainable production and the design of structurally optimized analogs.<\/jats:p>","DOI":"10.3390\/ph19030436","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T11:06:52Z","timestamp":1773054412000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Imperatorin: A Furanocoumarin with Potential in Combating Cancer Development and Progression\u2014A Comprehensive Review"],"prefix":"10.3390","volume":"19","author":[{"given":"Vict\u00f3ria Dogani","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia Rucco Penteado","family":"Detregiachi","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"dos Santos Bueno","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edza Santos","family":"de Argollo Haber","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel Gomes","family":"Eleut\u00e9rio","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"de Souza Bastos Mazuqueli Pereira","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virg\u00ednia Maria Cavallari Strozze","family":"Catharin","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidiane","family":"Indiani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor Cavallari Strozze","family":"Catharin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio Zabotto","family":"Dantas","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1tia Portero","family":"Sloan","sequence":"additional","affiliation":[{"name":"Department of Clinical Metabolism, Texas Institute for Kidney and Endocrine Disorders (TIKED), Lufkin, TX 75904, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Sergio Galina","family":"Spilla","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lance Alan","family":"Sloan","sequence":"additional","affiliation":[{"name":"Department of Clinical Metabolism, Texas Institute for Kidney and Endocrine Disorders (TIKED), Lufkin, TX 75904, USA"},{"name":"Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Quesada","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Graduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"},{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Fornari","family":"Laurindo","sequence":"additional","affiliation":[{"name":"Division of Cellular Growth, Hemodynamics, and Homeostasis Disorders, Graduate Program in Medical Sciences, Faculdade de Medicina, Universidade de S\u00e3o Paulo (USP), S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/s41392-024-01848-7","article-title":"Tumor initiation and early tumorigenesis: Molecular mechanisms and interventional targets","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Barbalho, S.M., Torres Pomini, K., Lima, E.P., da Silva Camarinha Oliveira, J., Boaro, B.L., Cressoni Ara\u00fajo, A., Landgraf Guiguer, E., Rici, R.E.G., Maria, D.A., and Haber, J. (2024). Fantastic Frogs and Where to Use Them: Unveiling the Hidden Cinobufagin\u2019s Promise in Combating Lung Cancer Development and Progression Through a Systematic Review of Preclinical Evidence. Cancers, 16.","DOI":"10.3390\/cancers16223758"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4950","DOI":"10.1002\/ptr.70057","article-title":"Catalpol: An Iridoid Glycoside With Potential in Combating Cancer Development and Progression-A Comprehensive Review","volume":"39","author":"Laurindo","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/JS9.0000000000001926","article-title":"Metabolic syndrome and cancer risk: A two-sample Mendelian randomization study of European ancestry","volume":"111","author":"Zhou","year":"2025","journal-title":"Int. J. Surg."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1007\/s00210-023-02792-z","article-title":"Exploring the logic and conducting a comprehensive evaluation of AdipoRon-based adiponectin replacement therapy against hormone-related cancers-a systematic review","volume":"397","author":"Laurindo","year":"2024","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1056\/NEJMoa2502098","article-title":"Medical Imaging and Pediatric and Adolescent Hematologic Cancer Risk","volume":"393","author":"Alber","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8075","DOI":"10.1007\/s00210-025-03902-9","article-title":"Cinobufagin: Unveiling the hidden bufadienolide\u2019s promise in combating alimentary canal cancer development and progression\u2014A comprehensive review","volume":"398","author":"Boaro","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s12967-025-06379-5","article-title":"Do cancer survivors have an increased risk of developing subsequent cancer? A population-based study","volume":"23","author":"Wang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1007\/s12672-025-02198-8","article-title":"Advancements and limitations in traditional anti-cancer therapies: A comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy","volume":"16","author":"Zafar","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_12","first-page":"270","article-title":"Nanoparticles in cancer therapy: Strategies to penetrate and modulate the tumor microenvironment\u2014A review","volume":"6","author":"Nguyen","year":"2025","journal-title":"Smart Mater. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e253469","DOI":"10.1001\/jamanetworkopen.2025.3469","article-title":"Comorbidity in Midlife and Cancer Outcomes","volume":"8","author":"Lavery","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123280","DOI":"10.1016\/j.lfs.2024.123280","article-title":"Isoorientin: Unveiling the hidden flavonoid\u2019s promise in combating cancer development and progression\u2014A comprehensive review","volume":"360","author":"Laurindo","year":"2025","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107430","DOI":"10.1016\/j.phrs.2024.107430","article-title":"The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review","volume":"209","author":"Laurindo","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_16","first-page":"308","article-title":"Cancer treatment and survivorship statistics, 2025","volume":"75","author":"Wagle","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e202402479","DOI":"10.1002\/cbdv.202402479","article-title":"Phytochemicals in Cancer Therapy: A Structured Review of Mechanisms, Challenges, and Progress in Personalized Treatment","volume":"22","author":"Aljabali","year":"2025","journal-title":"Chem. Biodivers."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Laurindo, L.F., de Maio, M.C., Minniti, G., de G\u00f3es Corr\u00eaa, N., Barbalho, S.M., Quesada, K., Guiguer, E.L., Sloan, K.P., Detregiachi, C.R.P., and Ara\u00fajo, A.C. (2023). Effects of Medicinal Plants and Phytochemicals in Nrf2 Pathways during Inflammatory Bowel Diseases and Related Colorectal Cancer: A Comprehensive Review. Metabolites, 13.","DOI":"10.3390\/metabo13020243"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"189241","DOI":"10.1016\/j.bbcan.2024.189241","article-title":"Promises of natural products as clinical applications for cancer","volume":"1880","author":"Deng","year":"2025","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s11418-025-01906-6","article-title":"Natural products that target p53 for cancer therapy","volume":"79","author":"Tsukamoto","year":"2025","journal-title":"J. Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1111\/bph.70014","article-title":"Natural products and cancer: From drug discovery to prevention and therapy","volume":"182","author":"Izzo","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1039\/D4RA05089D","article-title":"Incredible use of plant-derived bioactives as anticancer agents","volume":"15","author":"Kangra","year":"2025","journal-title":"RSC Adv."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hong, C.E., and Lyu, S.Y. (2025). Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26157247"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4604","DOI":"10.7150\/ijbs.113709","article-title":"Harnessing Natural Products to Surmount Drug Resistance in Gastric Cancer: Mechanisms and Therapeutic Perspectives","volume":"21","author":"Wang","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.32604\/or.2025.062778","article-title":"Clinically proven natural products against breast cancer, with mechanistic insights","volume":"33","author":"Hasan","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42145","DOI":"10.1038\/s41598-025-26010-3","article-title":"Decoding the anti-inflammatory properties of sesquiterpene coumarins from the active fractions of Ferula assa-foetida through integrated experimental and in silico analyses","volume":"15","author":"Alamri","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108790","DOI":"10.1016\/j.bioorg.2025.108790","article-title":"Coumarin-Chalcone derivatives as promising antioxidant agents targeting ischemia\/reperfusion injury through Nrf2 pathway activation","volume":"164","author":"Mohammadnia","year":"2025","journal-title":"Bioorg. Chem."},{"key":"ref_28","first-page":"88","article-title":"Biological Activity and Therapeutic Potential of Coumarin Derivatives: A Comprehensive Review","volume":"22","author":"Shristi","year":"2025","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"117088","DOI":"10.1016\/j.ejmech.2024.117088","article-title":"Exploring the anticancer potential and mechanisms of action of natural coumarins and isocoumarins","volume":"282","author":"Aqib","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17395","DOI":"10.1007\/s00210-025-04280-y","article-title":"Imperatorin as an activator of Nrf2\/ARE in mercury-induced brain damage based on rat model study, molecular docking, and molecular simulation approaches","volume":"398","author":"Murali","year":"2025","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s11101-016-9456-2","article-title":"Imperatorin-pharmacological meaning and analytical clues: Profound investigation","volume":"15","year":"2016","journal-title":"Phytochem. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100661","DOI":"10.1016\/j.prmcm.2025.100661","article-title":"Imperatorin suppresses NSCLC via interaction with PI3K\/AKT pathway and PD-L1: Computational and experimental evidence","volume":"16","author":"Xu","year":"2025","journal-title":"Pharmacol. Res. Mod. Chin. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1021\/ja01166a523","article-title":"Experiments with Xanthotoxin and Imperatorin Obtained from the Fruits of Ammi majus (L.)","volume":"72","author":"Sina","year":"1950","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.3892\/or.2016.4586","article-title":"Imperatorin exhibits anticancer activities in human colon cancer cells via the caspase cascade","volume":"35","author":"Zheng","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1159\/000331641","article-title":"Anticancer effects of imperatorin isolated from Angelica dahurica: Induction of apoptosis in HepG2 cells through both death-receptor- and mitochondria-mediated pathways","volume":"57","author":"Luo","year":"2011","journal-title":"Chemotherapy"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wu, Y., Xu, J., Liu, Y., Zeng, Y., and Wu, G. (2020). A Review on Anti-Tumor Mechanisms of Coumarins. Front Oncol., 10.","DOI":"10.3389\/fonc.2020.592853"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jep.2017.03.033","article-title":"Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1\u03b1 via the mTOR\/p70S6K\/4E-BP1 and MAPK pathways","volume":"203","author":"Mi","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1089\/ars.2019.7835","article-title":"Imperatorin Alleviates Psoriasiform Dermatitis by Blocking Neutrophil Respiratory Burst, Adhesion, and Chemotaxis Through Selective Phosphodiesterase 4 Inhibition","volume":"35","author":"Tsai","year":"2021","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"106612","DOI":"10.1016\/j.intimp.2020.106612","article-title":"Imperatorin suppresses IL-1\u03b2-induced iNOS expression via inhibiting ERK-MAPK\/AP1 signaling in primary human OA chondrocytes","volume":"85","author":"Ahmad","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.3892\/or.2017.5581","article-title":"Imperatorin efficiently blocks TNF-\u03b1-mediated activation of ROS\/PI3K\/Akt\/NF-\u03baB pathway","volume":"37","author":"Wang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/cns.13748","article-title":"Imperatorin inhibits mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and alleviates neuroinflammation in ischemic stroke","volume":"28","author":"Ge","year":"2022","journal-title":"CNS Neurosci. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5595","DOI":"10.1038\/s41598-022-21298-x","article-title":"Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway","volume":"13","author":"Liao","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Feng, Y., Zhang, M., Yuan, W., Zhao, D., Luo, Z., Tang, Z., Wang, Y., and Cang, M. (2025). Effects and Mechanisms of Imperatorin on Vitrified Mouse Oocytes. Animals, 15.","DOI":"10.3390\/ani15050661"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"173124","DOI":"10.1016\/j.ejphar.2020.173124","article-title":"Imperatorin: A review of its pharmacology, toxicity and pharmacokinetics","volume":"879","author":"Deng","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109401","DOI":"10.1016\/j.biopha.2019.109401","article-title":"Effects of imperatorin in the cardiovascular system and cancer","volume":"120","author":"Nasser","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0165-9936(96)00083-0","article-title":"Strategies for solid sample treatment","volume":"16","year":"1997","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4133","DOI":"10.3390\/molecules17044133","article-title":"Pressurized liquid extraction of coumarins from fruits of Heracleum leskowii with application of solvents with different polarity under increasing temperature","volume":"17","year":"2012","journal-title":"Molecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/pca.784","article-title":"Effect of extraction method on the yield of furanocoumarins from fruits of Archangelica officinalis Hoffm","volume":"15","author":"Petruczynik","year":"2004","journal-title":"Phytochem. Anal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jchromb.2003.07.006","article-title":"Influence of the extraction mode on the yield of some furanocoumarins from Pastinaca sativa fruits","volume":"800","author":"Petruczynik","year":"2004","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.seppur.2010.12.020","article-title":"A novel and efficient method combining SFE and liquid\u2013liquid extraction for separation of coumarins from Angelica dahurica","volume":"77","author":"Wang","year":"2011","journal-title":"Sep. Purif. Technol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/pca.870","article-title":"HPLC comparison of supercritical fluid extraction and solvent extraction of coumarins from the peel of Citrus maxima fruit","volume":"16","author":"Teng","year":"2005","journal-title":"Phytochem. Anal."},{"key":"ref_52","first-page":"1","article-title":"Extraction, isolation and characterization of bioactive compounds from plants\u2019 extracts","volume":"8","author":"Sasidharan","year":"2011","journal-title":"Afr. J. Tradit. Complement. Altern. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1365\/s10337-007-0185-y","article-title":"Isolation and Simultaneous Determination of Coumarin Compounds in Radix Angelica dahurica","volume":"65","author":"Wang","year":"2007","journal-title":"Chromatographia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chroma.2004.08.127","article-title":"Preparative isolation and purification of coumarins from Angelica dahurica (Fisch. ex Hoffm) Benth, et Hook. f (Chinese traditional medicinal herb) by high-speed counter-current chromatography","volume":"1052","author":"Liu","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.chroma.2004.10.091","article-title":"Preparative isolation and purification of bergapten and imperatorin from the medicinal plant Cnidium monnieri using high-speed counter-current chromatography by stepwise increasing the flow-rate of the mobile phase","volume":"1061","author":"Lia","year":"2004","journal-title":"J. Chromatogr. A"},{"key":"ref_56","first-page":"185","article-title":"Simultaneous determination of imperatorin and its metabolite xanthotoxol in rat plasma by using HPLC\u2013ESI-MS coupled with hollow fiber liquid phase microextraction","volume":"945\u2013946","author":"Zhang","year":"2014","journal-title":"J. Chromatogr. B"},{"key":"ref_57","first-page":"145","article-title":"Chapter 5\u2014Furanocoumarins: Biomolecules of Therapeutic Interest","volume":"Volume 43","year":"2014","journal-title":"Studies in Natural Products Chemistry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jchromb.2012.02.022","article-title":"Simultaneous determination of pimpinellin, isopimpinellin and phellopterin in rat plasma by a validated UPLC\u2013MS\/MS and its application to a pharmacokinetic study after administration of Toddalia asiatica extract","volume":"891\u2013892","author":"Liu","year":"2012","journal-title":"J. Chromatogr. B"},{"key":"ref_59","first-page":"7993","article-title":"Effects of isoimperatorin on proliferation and apoptosis of human gastric carcinoma cells","volume":"15","author":"Yang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"116691","DOI":"10.1016\/j.taap.2023.116691","article-title":"Phellopterin attenuates ovarian cancer proliferation and chemoresistance by inhibiting the PU.1\/CLEC5A\/PI3K-AKT feedback loop","volume":"477","author":"Guo","year":"2023","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wang, Y., Guan, T., Yue, X., Yang, J., Zhao, X., Chang, A., Yang, C., Fan, Z., Liu, K., and Li, Y. (2025). The biosynthetic pathway of coumarin and its genetic regulation in response to biotic and abiotic stresses. Front. Plant Sci., 16.","DOI":"10.3389\/fpls.2025.1599591"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.gce.2023.04.003","article-title":"Recent advances in the biosynthesis of coumarin and its derivatives","volume":"5","author":"Zou","year":"2024","journal-title":"Green Chem. Eng."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s42003-025-08076-x","article-title":"Integrative multi-omics data provide insights into the biosynthesis of furanocoumarins and mechanisms regulating their accumulation in Angelica dahurica","volume":"8","author":"Ji","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"154543","DOI":"10.1016\/j.jplph.2025.154543","article-title":"Cloning and functional study of AdOPT1, a gene for synthesizing isoimperatorin from Angelica dahurica var. formosana","volume":"311","author":"Nong","year":"2025","journal-title":"J. Plant Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"147757","DOI":"10.1016\/j.gene.2023.147757","article-title":"Transcriptome analysis provides insights into coumarin biosynthesis in the medicinal plant Angelica dahurica cv. Yubaizhi","volume":"888","author":"Zhang","year":"2023","journal-title":"Gene"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40529-018-0230-1","article-title":"Influence of harvest stage on the pharmacological effect of Angelica dahurica","volume":"59","author":"Liang","year":"2018","journal-title":"Bot. Stud."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"108396","DOI":"10.1016\/j.cclet.2023.108396","article-title":"Recent advances in the synthesis and applications of furocoumarin derivatives","volume":"34","author":"Chen","year":"2023","journal-title":"Chin. Chem. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"222","DOI":"10.2174\/1871523018666190625170802","article-title":"Psoralen Derivatives: Recent Advances of Synthetic Strategy and Pharmacological Properties","volume":"19","author":"Jamalis","year":"2020","journal-title":"Antiinflamm Antiallergy Agents Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1002\/ardp.201300259","article-title":"Synthesis of imperatorin analogs and their evaluation as acetylcholinesterase and butyrylcholinesterase inhibitors","volume":"346","author":"Granica","year":"2013","journal-title":"Arch. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"18","DOI":"10.2174\/157340611794072715","article-title":"Design, synthesis and preliminary evaluation of novel imperatorin derivatives as vasorelaxant agents","volume":"7","author":"Li","year":"2011","journal-title":"Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/bmc.3100","article-title":"Simultaneous determination of imperatorin and its metabolites in vitro and in vivo by a GC-MS method: Application to a bioavailability and protein binding ability study in rat plasma","volume":"28","author":"Zhao","year":"2014","journal-title":"Biomed. Chromatogr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1093\/jpp\/rgad127","article-title":"Elucidation the mechanism of the active ingredient imperatorin promoting drug absorption in cell model","volume":"76","author":"Ta","year":"2024","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.fitote.2013.01.007","article-title":"In vitro permeability analysis, pharmacokinetic and brain distribution study in mice of imperatorin, isoimperatorin and cnidilin in Radix Angelicae Dahuricae","volume":"85","author":"Lili","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Kwon, M.H., Jeong, J.S., Ryu, J., Cho, Y.W., and Kang, H.E. (2018). Pharmacokinetics and Brain Distribution of the Active Components of DA-9805, Saikosaponin A, Paeonol, and Imperatorin in Rats. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10030133"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"117155","DOI":"10.1016\/j.bcp.2025.117155","article-title":"Time-dependent inactivation of human cytochrome P450 2A6 variants and 2A13 by imperatorin: Natural coumarins and imperatorin oxidation","volume":"241","author":"Ueng","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_76","first-page":"1237","article-title":"[Inhibitory effect of imperatorin and isoimperatorin on activity of cytochrome P450 enzyme in human and rat liver microsomes]","volume":"38","author":"Cao","year":"2013","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Meng, D., Chen, F., Wu, Z., Wang, B., Wang, S., Geng, P., Dai, D., Zhou, Q., and Qiu, W. (2020). Inhibitory Effect of Imperatorin on the Pharmacokinetics of Diazepam In Vitro and In Vivo. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01079"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"102079","DOI":"10.1016\/j.jksus.2022.102079","article-title":"Identification of anticancer bioactive compounds derived from Ficus sp. by targeting Poly[ADP-ribose]polymerase 1 (PARP-1)","volume":"34","author":"Tabrez","year":"2022","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1080\/00207454.2019.1667789","article-title":"Anti-nociceptive and anti-inflammatory effect of imperatorin: Evidences for involvement of COX-2, iNOS, NF\u03baB and inflammatory cytokines","volume":"130","author":"Singh","year":"2020","journal-title":"Int. J. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1021\/acs.jnatprod.9b00145","article-title":"Anti-inflammatory Property of Imperatorin on Alveolar Macrophages and Inflammatory Lung Injury","volume":"82","author":"Li","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1021\/jf204297e","article-title":"Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory activity of imperatorin from Glehnia littoralis","volume":"60","author":"Huang","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"29868","DOI":"10.1021\/acsomega.2c02766","article-title":"Imperatorin Inhibits Proliferation, Migration, and Inflammation via Blocking the NF-\u03baB and MAPK Pathways in Rheumatoid Fibroblast-like Synoviocytes","volume":"7","author":"Lin","year":"2022","journal-title":"ACS Omega"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1007\/s10753-012-9495-9","article-title":"Imperatorin attenuates LPS-induced inflammation by suppressing NF-\u03baB and MAPKs activation in RAW 264.7 macrophages","volume":"35","author":"Guo","year":"2012","journal-title":"Inflammation"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"119291","DOI":"10.1016\/j.lfs.2021.119291","article-title":"Imperatorin alleviated endometriosis by inhibiting the activation of PI3K\/Akt\/NF-\u03baB pathway in rats","volume":"274","author":"Ma","year":"2021","journal-title":"Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Huang, M.H., Lin, Y.H., Lyu, P.C., Liu, Y.C., Chang, Y.S., Chung, J.G., Lin, W.Y., and Hsieh, W.T. (2021). Imperatorin Interferes with LPS Binding to the TLR4 Co-Receptor and Activates the Nrf2 Antioxidative Pathway in RAW264.7 Murine Macrophage Cells. Antioxidants, 10.","DOI":"10.3390\/antiox10030362"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1080\/09168451.2019.1710107","article-title":"Imperatorin alleviates ROS-mediated airway remodeling by targeting the Nrf2\/HO-1 signaling pathway","volume":"84","author":"Xian","year":"2020","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.physbeh.2013.08.019","article-title":"Effects of imperatorin on nicotine-induced anxiety- and memory-related responses and oxidative stress in mice","volume":"122","author":"Budzynska","year":"2013","journal-title":"Physiol. Behav."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"107170","DOI":"10.1016\/j.intimp.2020.107170","article-title":"Imperatorin reduces the inflammatory response of atherosclerosis by regulating MAPKs signaling pathway in vivo and in vitro","volume":"90","author":"Li","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/WNR.0000000000001997","article-title":"Imperatorin inhibits oxidative stress injury and neuroinflammation via the PI3K\/AKT signaling pathway in the MPTP-induced Parkinson\u2019s disease mouse","volume":"35","author":"Liu","year":"2024","journal-title":"Neuroreport"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1111\/bph.70210","article-title":"Imperatorin ameliorates metabolic dysfunction-associated fatty liver disease through modulating Suv39h1\/Fabps\/Cept1 signalling pathway","volume":"183","author":"Sun","year":"2026","journal-title":"Br. J. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.fitote.2013.07.007","article-title":"The protective activity of imperatorin in cultured neural cells exposed to hypoxia re-oxygenation injury via anti-apoptosis","volume":"90","author":"Wang","year":"2013","journal-title":"Fitoterapia"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wang, M., Xiao, Y., Miao, J., Zhang, X., Liu, M., Zhu, L., Liu, H., Shen, X., Wang, J., and Xie, B. (2025). Oxidative Stress and Inflammation: Drivers of Tumorigenesis and Therapeutic Opportunities. Antioxidants, 14.","DOI":"10.3390\/antiox14060735"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Brooks, A.J., and Putoczki, T. (2020). JAK-STAT Signalling Pathway in Cancer. Cancers, 12.","DOI":"10.3390\/cancers12071971"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s13277-015-3591-z","article-title":"Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy","volume":"37","author":"Hu","year":"2016","journal-title":"Tumor Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.canlet.2014.03.017","article-title":"Imperatorin induces Mcl-1 degradation to cooperatively trigger Bax translocation and Bak activation to suppress drug-resistant human hepatoma","volume":"348","author":"Li","year":"2014","journal-title":"Cancer Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1159\/000492874","article-title":"Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to \u03b3\u03b4-T Cell-Mediated Cytotoxicity","volume":"49","author":"You","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s11418-012-0719-y","article-title":"Imperatorin sensitizes anoikis and inhibits anchorage-independent growth of lung cancer cells","volume":"67","author":"Choochuay","year":"2013","journal-title":"J. Nat. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.pharep.2013.10.003","article-title":"The effect of quercetin and imperatorin on programmed cell death induction in T98G cells in vitro","volume":"66","author":"Langner","year":"2014","journal-title":"Pharmacol. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"236","DOI":"10.2174\/1874471015666220318122202","article-title":"Imperatorin Attenuates the Proliferation of MCF-7 Cells in Combination with Radiotherapy or Hyperthermia","volume":"15","author":"Amini","year":"2022","journal-title":"Curr. Radiopharm."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2000925","DOI":"10.1002\/advs.202000925","article-title":"Direct Targeting of CREB1 with Imperatorin Inhibits TGF\u03b22-ERK Signaling to Suppress Esophageal Cancer Metastasis","volume":"7","author":"Xu","year":"2020","journal-title":"Adv. Sci."},{"key":"ref_102","first-page":"1471","article-title":"Imperatorin shows selective antitumor effects in SGC-7901 human gastric adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting PI3K\/Akt\/m-TOR signalling pathway","volume":"22","author":"Am","year":"2017","journal-title":"J. BUON"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1186\/s12935-021-02397-7","article-title":"Imperatorin induces autophagy and G0\/G1 phase arrest via PTEN-PI3K-AKT-mTOR\/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo","volume":"21","author":"Lv","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wu, C.P., Murakami, M., Li, Y.C., Huang, Y.H., Chang, Y.T., Hung, T.H., Wu, Y.S., and Ambudkar, S.V. (2023). Imperatorin Restores Chemosensitivity of Multidrug-Resistant Cancer Cells by Antagonizing ABCG2-Mediated Drug Transport. Pharmaceuticals, 16.","DOI":"10.3390\/ph16111595"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4196\/kjpp.2022.26.3.145","article-title":"Chemosensitizing effect and mechanism of imperatorin on the anti-tumor activity of doxorubicin in tumor cells and transplantation tumor model","volume":"26","author":"Liang","year":"2022","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"236","DOI":"10.2174\/1871520614666140922122358","article-title":"Growth inhibition of various human cancer cell lines by imperatorin and limonin from poncirus trifoliata rafin","volume":"15","author":"Rahman","year":"2015","journal-title":"Seeds. Anticancer Agents Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Grabarska, A., Skalicka-Wo\u017aniak, K., Kie\u0142bus, M., Dmoszy\u0144ska-Graniczka, M., Miziak, P., Szumi\u0142o, J., Nowosadzka, E., Kowalczuk, K., Khalifa, S., and Smok-Kalwat, J. (2020). Imperatorin as a Promising Chemotherapeutic Agent Against Human Larynx Cancer and Rhabdomyosarcoma Cells. Molecules, 25.","DOI":"10.3390\/molecules25092046"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11010-014-2032-4","article-title":"Combined treatment with quercetin and imperatorin as a potent strategy for killing HeLa and Hep-2 cells","volume":"392","author":"Paduch","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_109","first-page":"e72239","article-title":"Recent Trends in Liver Cancer: Epidemiology, Risk Factors, and Diagnostic Techniques","volume":"16","author":"Kale","year":"2024","journal-title":"Cureus"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2011.12.061","article-title":"Epidemiology of viral hepatitis and hepatocellular carcinoma","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"543","DOI":"10.6004\/jnccn.2015.0074","article-title":"Diagnostic delays are common among patients with hepatocellular carcinoma","volume":"13","author":"Patel","year":"2015","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.3748\/wjg.v30.i19.2488","article-title":"Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice","volume":"30","author":"Bombassaro","year":"2024","journal-title":"World J. Gastroenterol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/s41417-024-00764-w","article-title":"Heterogeneity of hepatocellular carcinoma: From mechanisms to clinical implications","volume":"31","author":"Safri","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"104","DOI":"10.12688\/f1000research.145493.2","article-title":"Hepatocellular carcinoma: Advances in systemic therapies","volume":"13","author":"Wu","year":"2024","journal-title":"F1000Res"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3350\/cmh.2020.0016","article-title":"Substantial risk of recurrence even after 5 recurrence-free years in early-stage hepatocellular carcinoma patients","volume":"26","author":"Kim","year":"2020","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e165\u2013172","DOI":"10.1016\/S1470-2045(14)71180-5","article-title":"Transformation from non-small-cell lung cancer to small-cell lung cancer: Molecular drivers and cells of origin","volume":"16","author":"Oser","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.lungcan.2006.12.016","article-title":"Differences between small-cell lung cancer and non-small-cell lung cancer among tobacco smokers","volume":"56","author":"Toh","year":"2007","journal-title":"Lung Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"358","DOI":"10.21037\/atm-22-4444","article-title":"Developments in targeted therapy & immunotherapy-how non-small cell lung cancer management will change in the next decade: A narrative review","volume":"11","author":"Li","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1097\/CM9.0000000000002529","article-title":"Global burden and trends of lung cancer incidence and mortality","volume":"136","author":"Li","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1038\/s41416-025-03139-6","article-title":"Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: Insights from multi-omics studies","volume":"133","author":"Rocca","year":"2025","journal-title":"Br. J. Cancer"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"22445","DOI":"10.1038\/s41598-024-73389-6","article-title":"Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using SEER database","volume":"14","author":"Xie","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"21501319241235011","DOI":"10.1177\/21501319241235011","article-title":"Inadequate Uptake of USPSTF-Recommended Low Dose CT Lung Cancer Screening","volume":"15","author":"Sorscher","year":"2024","journal-title":"J. Prim. Care Community Health"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s40478-023-01605-x","article-title":"On the origin and development of glioblastoma: Multifaceted role of perivascular mesenchymal stromal cells","volume":"11","author":"Khettab","year":"2023","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Seker-Polat, F., Pinarbasi Degirmenci, N., Solaroglu, I., and Bagci-Onder, T. (2022). Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives. Cancers, 14.","DOI":"10.3390\/cancers14020443"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Balzano, E., Di Tommaso, E., Antoccia, A., Pelliccia, F., and Giunta, S. (2021). Characterization of Chromosomal Instability in Glioblastoma. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.810793"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11060-025-05282-9","article-title":"EGFR pathway alterations correlate with rapid early progression in glioblastoma","volume":"176","author":"Samimi","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.5603\/RPOR.a2022.0113","article-title":"Survival and quality of life analysis in glioblastoma multiforme with adjuvant chemoradiotherapy: A retrospective study","volume":"27","author":"Mohammed","year":"2022","journal-title":"Rep. Pr. Oncol. Radiother."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1124\/dmd.112.048322","article-title":"Function of the blood-brain barrier and restriction of drug delivery to invasive glioma cells: Findings in an orthotopic rat xenograft model of glioma","volume":"41","author":"Agarwal","year":"2013","journal-title":"Drug Metab. Dispos."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s44385-025-00033-x","article-title":"Interstitial fluid transport dynamics predict glioblastoma invasion and progression","volume":"2","author":"Stine","year":"2025","journal-title":"npj Biomed. Innov."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.3390\/curroncol31070296","article-title":"Temozolomide (TMZ) in the Treatment of Glioblastoma Multiforme-A Literature Review and Clinical Outcomes","volume":"31","author":"Nafalska","year":"2024","journal-title":"Curr. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Smerdi, D., Moutafi, M., Kotsantis, I., Stavrinou, L.C., and Psyrri, A. (2024). Overcoming Resistance to Temozolomide in Glioblastoma: A Scoping Review of Preclinical and Clinical Data. Life, 14.","DOI":"10.3390\/life14060673"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"138","DOI":"10.5306\/wjco.v14.i4.138","article-title":"Immunotherapy in glioblastoma treatment: Current state and future prospects","volume":"14","author":"Lemos","year":"2023","journal-title":"World J. Clin. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/CMR.16.1.1-17.2003","article-title":"Human papillomavirus and cervical cancer","volume":"16","author":"Burd","year":"2003","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.3892\/ol.2020.11754","article-title":"Cervical cancer in low and middle-income countries","volume":"20","author":"Hull","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1002296","DOI":"10.37349\/etat.2025.1002296","article-title":"Immunotherapy in cervical cancer: An innovative approach for better treatment outcomes","volume":"6","author":"Dey","year":"2025","journal-title":"Explor. Target. Antitumor Ther."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Tekalign, T., and Teshome, M. (2022). Prevalence and determinants of late-stage presentation among cervical cancer patients, a systematic review and meta-analysis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267571"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"102369","DOI":"10.1016\/j.canep.2023.102369","article-title":"Use of risk-based cervical screening programs in resource-limited settings","volume":"84","author":"Perkins","year":"2023","journal-title":"Cancer Epidemiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"100579","DOI":"10.1016\/j.esmoop.2022.100579","article-title":"Recurrent or primary metastatic cervical cancer: Current and future treatments","volume":"7","author":"Gennigens","year":"2022","journal-title":"ESMO Open"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/ijgo.70276","article-title":"Strategic approaches for global cervical cancer elimination: An update review and call for national action","volume":"171","author":"Wilailak","year":"2025","journal-title":"Int. J. Gynaecol. Obs."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Sancha, N., Corchado-Cobos, R., and P\u00e9rez-Losada, J. (2025). Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26072993"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/s41586-025-09869-0","article-title":"Fasting boosts breast cancer therapy efficacy via glucocorticoid activation","volume":"649","author":"Severson","year":"2026","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/s41571-024-00924-9","article-title":"HER2-targeted therapies beyond breast cancer\u2014An update","volume":"21","author":"Yoon","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1159\/000363755","article-title":"Chemotherapy in early breast cancer: When, how and which one?","volume":"9","author":"Schmidt","year":"2014","journal-title":"Breast Care (Basel)"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"100210","DOI":"10.1016\/j.medidd.2025.100210","article-title":"Understanding drug resistance in breast cancer: Mechanisms and emerging therapeutic strategies","volume":"26","author":"Gautam","year":"2025","journal-title":"Med. Drug Discov."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s12672-025-02227-6","article-title":"A comprehensive review on targeted therapies for triple negative breast cancer: An evidence-based treatment guideline","volume":"16","author":"Emara","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"8040","DOI":"10.1245\/s10434-024-15895-5","article-title":"Financial Toxicity Among Women with Breast Cancer Varies by Age and Race","volume":"31","author":"Myers","year":"2024","journal-title":"Ann. Surg. Oncol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/s41598-023-27578-4","article-title":"Racial disparities in breast cancer treatment patterns and treatment related adverse events","volume":"13","author":"Stabellini","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Majmudar, V.H., Nguyen-Ngo, K., and Tadros, M. (2025). Divergent Trends in Esophageal Adenocarcinoma and Squamous Cell Carcinoma Incidence, 2000\u20132022. Gastroenterol. Insights, 16.","DOI":"10.20944\/preprints202508.1507.v1"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"563","DOI":"10.4081\/jphia.2017.563","article-title":"Prevalence of Squamous Cell Carcinoma of the Esophagus in a Single Tertiary Center of South Africa: A Cross Sectional Analytic Study","volume":"8","author":"Kgomo","year":"2017","journal-title":"J. Public Health Afr."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"E218","DOI":"10.1055\/a-2221-7974","article-title":"Trends in prevalence of esophageal adenocarcinoma: Findings from a statewide database of over 6 million patients","volume":"12","author":"Qumseya","year":"2024","journal-title":"Endosc. Int. Open"},{"key":"ref_151","first-page":"CD010511","article-title":"Chemoradiotherapy versus chemoradiotherapy plus surgery for esophageal cancer","volume":"8","author":"Vellayappan","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yang, W., Wang, Q., and Zhou, Y. (2023). Mechanisms of esophageal cancer metastasis and treatment progress. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1206504"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1002\/ijc.35314","article-title":"Considerations to forgo systemic treatment in patients with advanced esophageal or gastric cancer: A real-world evidence study","volume":"156","author":"Slotman","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1016\/j.jtcvs.2009.07.069","article-title":"Recurrence after neoadjuvant chemoradiation and surgery for esophageal cancer: Does the pattern of recurrence differ for patients with complete response and those with partial or no response?","volume":"138","author":"Meguid","year":"2009","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s40139-013-0009-8","article-title":"Helicobacter, Inflammation, and Gastric Cancer","volume":"1","author":"Sepulveda","year":"2013","journal-title":"Curr. Pathobiol. Rep."},{"key":"ref_156","first-page":"669","article-title":"Eastern European and Asian-born populations are prone to gastric cancer: An epidemiologic analysis of foreign-born populations and gastric cancer","volume":"34","author":"Kumar","year":"2021","journal-title":"Ann. Gastroenterol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/S0140-6736(09)60617-6","article-title":"Gastric cancer","volume":"374","author":"Hartgrink","year":"2009","journal-title":"Lancet"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/jso.26844","article-title":"Advances in screening and detection of gastric cancer","volume":"125","author":"Xia","year":"2022","journal-title":"J. Surg. Oncol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Chen, Y., Sun, Z., Chen, W., Liu, C., Chai, R., Ding, J., Liu, W., Feng, X., Zhou, J., and Shen, X. (2021). The Immune Subtypes and Landscape of Gastric Cancer and to Predict Based on the Whole-Slide Images Using Deep Learning. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.685992"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Dahiya, D.S., Malik, S., Paladiya, R., Ahsan, S., Wasim, H., Bharadwaj, H.R., Goel, A., Jaan, A., Hayat, U., and Hasan, F. (2025). Advances in Non-Invasive Screening Methods for Gastrointestinal Cancers: How Continued Innovation Has Revolutionized Early Cancer Detection. Cancers, 17.","DOI":"10.3390\/cancers17071085"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1038\/s43018-024-00841-x","article-title":"Recapitulating the adenoma\u2013carcinoma sequence by selection of four spontaneous oncogenic mutations in mismatch-repair-deficient human colon organoids","volume":"5","author":"Mizutani","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s13668-025-00701-9","article-title":"Nutrition, Environment, and Genetics in Colorectal Cancer. Epigenetics and Possible Future Perspective","volume":"14","author":"Brandolino","year":"2025","journal-title":"Curr. Nutr. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1470-2045(24)00600-4","article-title":"Colorectal cancer incidence trends in younger versus older adults: An analysis of population-based cancer registry data","volume":"26","author":"Sung","year":"2025","journal-title":"Lancet Oncol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"104775","DOI":"10.1016\/j.critrevonc.2025.104775","article-title":"Immunotherapy in microsatellite-stable colorectal cancer: Strategies to overcome resistance","volume":"212","author":"Chen","year":"2025","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Haynes, J., and Manogaran, P. (2025). Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26051988"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.gie.2024.03.010","article-title":"Contributions of early detection and cancer prevention to colorectal cancer mortality reduction by screening colonoscopy: A validated modeling study","volume":"100","author":"Heisser","year":"2024","journal-title":"Gastrointest. Endosc."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1001\/jama.2021.0106","article-title":"Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review","volume":"325","author":"Biller","year":"2021","journal-title":"Jama"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1111\/ans.19221","article-title":"Challenges around diagnosis of early onset colorectal cancer, and the case for screening","volume":"94","author":"Waddell","year":"2024","journal-title":"ANZ J. Surg."},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"El Motassime, A., Vitiello, R., Comodo, R.M., Capece, G., Bocchino, G., Bocchi, M.B., Maccauro, G., and Meschini, C. (2025). Osteosarcoma: A Comprehensive Morphological and Molecular Review with Prognostic Implications. Biology, 14.","DOI":"10.3390\/biology14101407"},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Breden, S., Beischl, S., Hinterwimmer, F., Consalvo, S., Knebel, C., von Eisenhart-Rothe, R., Burgkart, R., and Lenze, U. (2025). Surgical Margin Analysis in Osteosarcoma: Impact on Survival and Local Control. Cancers, 17.","DOI":"10.3390\/cancers17152581"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"20125","DOI":"10.1038\/s41598-023-47412-1","article-title":"Modeling phenotypic heterogeneity towards evolutionarily inspired osteosarcoma therapy","volume":"13","author":"Welch","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_172","first-page":"e20210478","article-title":"Pulmonary metastasis of osteosarcoma: Multiple presentations in a single patient","volume":"48","author":"Silva","year":"2022","journal-title":"J. Bras. Pneumol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1002324","DOI":"10.37349\/etat.2025.1002324","article-title":"Osteosarcoma: Current insights and advances","volume":"6","author":"Brar","year":"2025","journal-title":"Explor. Target. Antitumor Ther."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Han, Z., Chen, G., and Wang, D. (2025). Emerging immunotherapies in osteosarcoma: From checkpoint blockade to cellular therapies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1579822"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"831","DOI":"10.2147\/IJN.S150086","article-title":"Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery","volume":"13","author":"Lin","year":"2018","journal-title":"Int J Nanomed."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S2707-3688(23)00022-5","article-title":"Comparative study of liposomes and liposomes-in-polymer hydrogel as transdermal carriers for improving the topical delivery of imperatorin","volume":"2","author":"Ban","year":"2021","journal-title":"J. Holist. Integr. Pharm."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Liang, X., Chen, X., Zhao, G., Tang, T., Dong, W., Wang, C., Zhang, J., and Liao, Z. (2018). Preparation, Characterization, and Pharmacokinetic Evaluation of Imperatorin Lipid Microspheres and Their Effect on the Proliferation of MDA-MB-231 Cells. 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