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s41698-025-01106-1.pdf (3.87 MB)

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2025-11-07

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cc-by-nc-nd (c) Martínez Jañez, Noelia et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/224911

Co-clinical trial targeting ER, FGFR and CDK4/6 in resistant hormone-positive breast cancer with FGFR alterations

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Recurs relacionat

https://doi.org/10.1038/s41698-025-01106-1

Resum

Management of advanced hormone receptor-positive, HER2-negative breast cancer after progression on endocrine therapy plus CDK4/6 inhibitors is challenging due to mutational heterogeneity. Current therapies yield limited efficacy, achieving 4-6 months PFS. FGFR signaling is implicated in resistance to endocrine plus CDK4/6 inhibitors, but FGFR inhibitors have shown limited activity in unselected populations. Co-clinical trials bridge preclinical and clinical findings, optimize resources, and enable biomarker identification. Using patient-derived organoids (PDOs), we demonstrated that FGFR-amplified PDOs respond to fulvestrant, palbociclib, and rogaratinib only when PIK3CA and ESR1 are wild-type. In a dose-escalation trial pre-screening 66 patients with FGFR1/2-amplification (FISH) and/or overexpression (RNAScope) patients, >40% harbored FGFR alterations. Nine patients were enrolled; the combination showed activity specifically in PIK3CA- and ESR1-wild type patients (9.1 vs. 1.9 months PFS; P = 0.0005). Toxicity was manageable and consistent with prior data. Our findings highlight biomarker-driven approaches as essential for refining FGFR-targeted strategies in this resistant population.

Matèries

Hormonoteràpia, Assaigs clínics, Oncologia

Matèries (anglès)

Hormone therapy, Clinical trials, Oncology

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

MARTÍNEZ JAÑEZ, Noelia, et al. Co-clinical trial targeting ER, FGFR and CDK4/6 in resistant hormone-positive breast cancer with FGFR alterations. Precision Oncology. 2025. Vol. 9, num. 343. ISSN 2056-3973. [consulted: 21 of August of 2026]. Available at: https://hdl.handle.net/2445/224911

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