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oai:recercat.cat:2445/1301192025-12-05T09:23:17Zcom_2072_1057col_2072_478799col_2072_478858col_2072_478916col_2072_478908col_2072_478917

Resistance to taxanes in triple negative breast cancer associates with the dynamics of a CD49f+ tumor initiating population Gómez Miragaya, Jorge Palafox Sánchez, Marta Paré, Laia Yoldi, Guillermo Ferrer, Irene Vila, Sergi Galván, Patricia Pellegrini, Pasquale Pérez-Montoyo, Hector Igea, Ana Muñoz Moruno, Purificación Esteller, Manel Nebreda, Àngel R. Urruticoechea Ribate, Ander Morilla, Idoia Pernas, Sònia Climent, Fina Soler, María Teresa Petit, Anna Serra Elizalde, Violeta Prat Aparicio, Aleix González Suárez, Eva Medicaments antineoplàstics Ús terapèutic Resistència als medicaments Metabolisme Integrines Càncer de mama Antineoplastic agents Therapeutic use Drug resistance Metabolism Integrins Breast cancer 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. 2019-03-12T11:56:23Z 2019-03-12T11:56:23Z 2017-05 2019-03-12T11:56:23Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 2213-6711 https://hdl.handle.net/2445/130119 673483 28457887 eng Reproducció del document publicat a: https://doi.org/10.1016/j.stemcr.2017.03.026 Stem Cell Reports, 2017, vol. 8, num. 5, p. 1392-1407 https://doi.org/10.1016/j.stemcr.2017.03.026 cc-by (c) Gómez Miragaya, Jorge et al., 2017 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess 16 p. application/pdf Elsevier Articles publicats en revistes (Ciències Fisiològiques)