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Cellular senescence and its associated secretory phenotype (SASP) can have multiple tumor-promoting activities, but both are largely unexplored in these cancers. In this study, using xenograft, orthotopic and Kras\n                    <jats:sup>G12V<\/jats:sup>\n                    -driven murine NSCLC models, we demonstrate that cisplatin-induced senescence strongly promotes malignant phenotypes and tumor progression, which is stimulated by aging. Mechanistically, we found that a transforming growth factor-beta (TGF\u03b2)-enriched SASP drives pro-proliferative effects through TGFBR1 and AKT\/mTOR. TGFBR1 inhibition with galunisertib or senolytic treatment reduces tumor progression driven by cisplatin-induced senescence, and concomitant use of TGFBR1 inhibitors with platinum-based chemotherapy reduces tumor burden and improves survival. Finally, we validate the translational relevance of tumor-promoting TGF\u03b2-enriched SASP using clinical NSCLC and HGSOC samples from patients who received neoadjuvant platinum-based chemotherapy. Together, our findings identify a potential cancer therapy resistance mechanism and provide preclinical proof of concept for future trials.\n                  <\/jats:p>","DOI":"10.1038\/s43587-025-01054-2","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T10:03:07Z","timestamp":1770112987000},"page":"368-392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Treatment resistance to platinum-based chemotherapy in lung and ovarian cancer is driven by a targetable TGF\u03b2 senescent secretome"],"prefix":"10.1038","volume":"6","author":[{"given":"Estela","family":"Gonz\u00e1lez-Gualda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika A. 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