Gómez Miragaya, JorgePalafox Sánchez, MartaParé, LaiaYoldi, GuillermoFerrer, IreneVila, SergiGalván, PatriciaPellegrini, PasqualePérez-Montoyo, HectorIgea, AnaMuñoz Moruno, PurificaciónEsteller, ManelNebreda, Àngel R.Urruticoechea Ribate, AnderMorilla, IdoiaPernas, SòniaCliment, FinaSoler, María TeresaPetit, AnnaSerra Elizalde, VioletaPrat Aparicio, AleixGonzález Suárez, Eva2019-03-122019-03-122017-052213-6711https://hdl.handle.net/2445/130119Taxanes 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.16 p.application/pdfengcc-by (c) Gómez Miragaya, Jorge et al., 2017http://creativecommons.org/licenses/by/3.0/esMedicaments antineoplàsticsÚs terapèuticResistència als medicamentsMetabolismeIntegrinesCàncer de mamaAntineoplastic agentsTherapeutic useDrug resistanceMetabolismIntegrinsBreast cancerinfo:eu-repo/semantics/article6734832019-03-12info:eu-repo/semantics/openAccess28457887