Títol:
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Resistance to taxanes in triple negative breast cancer associates with the dynamics of a CD49f+ tumor initiating population
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Autor/a:
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Gómez Miragaya, Jorge; Palafox Sánchez, Marta; Paré Brunet, 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
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Notes:
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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. |
Matèries:
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-Medicaments antineoplàstics -Ús terapèutic -Resistència als medicaments -Metabolisme -Integrines -Càncer de mama -Antineoplastic agents -Therapeutic use -Drug resistance -Metabolism -Integrins -Breast cancer |
Drets:
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cc-by (c) Gómez Miragaya, Jorge et al., 2017
http://creativecommons.org/licenses/by/3.0/es
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Tipus de document:
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Article Article - Versió publicada |
Publicat per:
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Elsevier
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