{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:03:34Z","timestamp":1792994614759,"version":"4.5.0"},"reference-count":123,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Coumarin derivatives constitute a versatile small-molecule chemotype with broad anticancer potential. This narrative review synthesizes recent in vitro and in vivo evidence on coumarin-based scaffolds, emphasizing breast cancer and covering lung, prostate, and colorectal models. We summarize major mechanisms of action\u2014including induction of apoptosis (caspase activation and BAX\/BCL-2 balance), modulation of PI3K\/Akt\/mTOR signaling, inhibition of angiogenesis (VEGFR-2), interference with estrogen biosynthesis (aromatase\/ER axis), chaperone targeting (Hsp90), and attenuation of multidrug resistance (efflux pumps\/autophagy)\u2014and highlight representative chemotypes (e.g., benzimidazole, triazole, furocoumarins, topoisomerase- and CDK-oriented hybrids). Where available, we contrast potency and selectivity across models (e.g., MCF-7 vs. MDA-MB-231; A549; PC-3; colon lines) and discuss structure\u2013activity trends linking substituent patterns (heteroaryl linkers, judicious halogenation, polar handles) to pathway engagement. We also delineate translational gaps limiting clinical progress\u2014selectivity versus non-malignant cells, incomplete pharmacokinetic and safety characterization, and limited validation beyond xenografts. Finally, we outline priorities for preclinical optimization: biology-aligned target selection with biomarkers, resistance-aware combinations (e.g., PI3K\/mTOR \u00b1 autophagy modulation; MDR mitigation), and early integration of ADME\/tox and PK\/PD to confirm on-target exposure. Collectively, the evidence supports coumarins as adaptable, multi-target anticancer leads, particularly promising in hormone-dependent breast cancer while remaining relevant to other tumor types.<\/jats:p>","DOI":"10.3390\/molecules30214167","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:35:11Z","timestamp":1761269711000},"page":"4167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Coumarin Derivatives as Anticancer Agents: Mechanistic Landscape with an Emphasis on Breast Cancer"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5739-9783","authenticated-orcid":false,"given":"Veda B.","family":"Hacholli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nitte College of Pharmaceutical Sciences, Nitte (Deemed to be University), Bengaluru 560064, KA, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubha M.","family":"R.","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nitte College of Pharmaceutical Sciences, Nitte (Deemed to be University), Bengaluru 560064, KA, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prabhanajan B.","family":"H.","sequence":"additional","affiliation":[{"name":"ITAAN PHARMA PVT. Ltd., Plot No S-9, Genome Valley Phase III, Biotech Park, Karkapatla 5022812, TG, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavanya","family":"M.","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nitte College of Pharmaceutical Sciences, Nitte (Deemed to be University), Bengaluru 560064, KA, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pramod","family":"S.","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nitte College of Pharmaceutical Sciences, Nitte (Deemed to be University), Bengaluru 560064, KA, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 560064, KA, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-3797","authenticated-orcid":false,"given":"\u0141ukasz","family":"Szeleszczuk","sequence":"additional","affiliation":[{"name":"Department of Organic and Physical Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1 Street, PL-02093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9176-7108","authenticated-orcid":false,"given":"Marcin","family":"Gackowski","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Bromatology, Faculty of Pharmacy, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, A. Jurasza 2 Street, PL-85089 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 Cancer Estimates: Data Sources, Methods, and a Snapshot of the Cancer Burden Worldwide","volume":"156","author":"Filho","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_2","first-page":"77","article-title":"Latest Updates in Coumarin Scaffolds as Potent Antiproliferative Agents (2018\u20132023)","volume":"9","author":"Elshemy","year":"2025","journal-title":"Sphinx J. Pharm. Med. 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