{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:47:28Z","timestamp":1790034448622,"version":"4.0.1"},"reference-count":275,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad UTE"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their potential to enhance the efficacy of standard chemotherapy and reduce resistance-related mechanisms. We also highlight innovative strategies, including combination therapies and advanced drug delivery systems, that aim to improve their clinical applicability. Overall, this work underscores the relevance of integrating natural bioactives into modern cancer therapy and calls for further translational research to bridge preclinical findings with clinical implementation.<\/jats:p>","DOI":"10.3390\/ijms26168037","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"8037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer\u2013Tumor Microenvironment Interface"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4234-5524","authenticated-orcid":false,"given":"Claudia","family":"Reytor-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9670-6376","authenticated-orcid":false,"given":"Emilia","family":"Jim\u00e9nez-Flores","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9327-2723","authenticated-orcid":false,"given":"Natal\u00ed","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Odontolog\u00eda, Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3641-1501","authenticated-orcid":false,"given":"Daniel","family":"Simancas-Racines","sequence":"additional","affiliation":[{"name":"Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigaci\u00f3n en Salud P\u00fablica y Epidemiolog\u00eda Cl\u00ednica (CISPEC), Quito 170527, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dakal, T.C., Sharma, N.K., and Sharma, A. 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