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

• Published in: Stem cell reports
• Main Authors: 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, Violeta, Prat Aparicio, Aleix, González Suárez, Eva
• Format: Journal Article
• Language: English
• Published: Elsevier 01-05-2017
• Subjects: Antineoplastic agents; Breast cancer; Càncer de mama; Drug resistance; Integrines; Integrins; Medicaments antineoplàstics; Metabolism; Metabolisme; Resistència als medicaments; Therapeutic use; Ús terapèutic
• ISSN: 2213-6711; 2213-6711

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.