| Autor: |
Jorge Gómez-Miragaya, Marta Palafox, Laia Paré, Guillermo Yoldi, Irene Ferrer, Sergi Vila, Patricia Galván, Pasquale Pellegrini, Hector Pérez-Montoyo, Ana Igea, Purificación Muñoz, Manel Esteller, Angel R. Nebreda, Ander Urruticoechea, Idoia Morilla, Sonia Pernas, Fina Climent, María Teresa Soler-Monso, Ana Petit, Violeta Serra, Aleix Prat, Eva González-Suárez |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
|
| Zdroj: |
Stem Cell Reports, Vol 8, Iss 5, Pp 1392-1407 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2213-6711 |
| DOI: |
10.1016/j.stemcr.2017.03.026 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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