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2017-05

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cc-by (c) Gómez Miragaya, Jorge et al., 2017
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/130119

Resistance to taxanes in triple negative breast cancer associates with the dynamics of a CD49f+ tumor initiating population

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https://doi.org/10.1016/j.stemcr.2017.03.026

Abstract

Taxanes are a mainstay of treatment for breast cancer, but resistance often develops followed by metastatic disease and mortality. Aiming to reveal the mechanisms underlying taxane resistance, we used breast cancer patient-derived orthoxenografts (PDX). Mimicking clinical behavior, triple-negative breast tumors (TNBCs) from PDX models were more sensitive to docetaxel than luminal tumors, but they progressively acquired resistance upon continuous drug administration. Mechanistically, we found that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands during the acquisition of drug resistance. In the absence of the drug, the resistant CD49f+ population shrinks and taxane sensitivity is restored. We describe a transcriptional signature of resistance, predictive of recurrent disease after chemotherapy in TNBC. Together, these findings identify a CD49f+ population enriched in tumor-initiating ability and chemoresistance properties and evidence a drug holiday effect on the acquired resistance to docetaxel in triple-negative breast cancer.

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Medicaments antineoplàstics, Ús terapèutic, Resistència als medicaments, Metabolisme, Integrines, Càncer de mama

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Antineoplastic agents, Therapeutic use, Drug resistance, Metabolism, Integrins, Breast cancer

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

Citation

GÓMEZ MIRAGAYA, Jorge, et al. Resistance to taxanes in triple negative breast cancer associates with the dynamics of a CD49f+ tumor initiating population. Stem Cell Reports. 2017. Vol. 8, num. 5, pags. 1392-1407. ISSN 2213-6711. [consulted: 12 of June of 2026]. Available at: https://hdl.handle.net/2445/130119

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