Resistance to Taxanes in Triple-Negative Breast Cancer Associates with the Dynamics of a CD49f+ Tumor-Initiating Population.

Autor:	Gómez-Miragaya J; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Palafox M; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Paré L; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain., Yoldi G; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Ferrer I; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Vila S; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Galván P; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain., Pellegrini P; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Pérez-Montoyo H; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Igea A; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain., Muñoz P; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain., Esteller M; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain; Unitat de Bioquímica i Biologia Molecular, Departament de Ciències Fisiològiques II, Universitat de Barcelona-IDIBELL, 08908 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain., Nebreda AR; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain., Urruticoechea A; Breast Cancer Unit, Catalan Institute of Oncology, IDIBELL, 08908 Barcelona, Spain., Morilla I; Breast Cancer Unit, Catalan Institute of Oncology, IDIBELL, 08908 Barcelona, Spain., Pernas S; Breast Cancer Unit, Catalan Institute of Oncology, IDIBELL, 08908 Barcelona, Spain., Climent F; Pathology Department, University Hospital of Bellvitge, IDIBELL, 08908 Barcelona, Spain., Soler-Monso MT; Pathology Department, University Hospital of Bellvitge, IDIBELL, 08908 Barcelona, Spain., Petit A; Pathology Department, University Hospital of Bellvitge, IDIBELL, 08908 Barcelona, Spain., Serra V; Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain., Prat A; Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), 08035 Barcelona, Spain., González-Suárez E; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Avinguda de la Gran Via, 199 - 203, L'Hospitalet de Llobregat, 08908 Barcelona, Spain. Electronic address: egsuarez@idibell.cat.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2017 May 09; Vol. 8 (5), pp. 1392-1407. Date of Electronic Publication: 2017 Apr 27.
DOI:	10.1016/j.stemcr.2017.03.026
Abstrakt:	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. (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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