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

Autor: María Teresa Soler-Monso, Violeta Serra, Manel Esteller, Marta Palafox, Héctor Pérez-Montoyo, Ana Igea, Jorge Gomez-Miragaya, Eva González-Suárez, Sergi Vila, Ana Petit, Ander Urruticoechea, Purificación Muñoz, Aleix Prat, Guillermo Yoldi, Sonia Pernas, Idoia Morilla, Fina Climent, Irene Ferrer, Laia Paré, Angel R. Nebreda, Patricia Galván, Pasquale Pellegrini
Přispěvatelé: Universitat de Barcelona
Předmět:
0301 basic medicine
Integrins
medicine.medical_treatment
Triple Negative Breast Neoplasms
Drug resistance
drug holidays
Docetaxel
Pharmacology
Integrin alpha6
Biochemistry
Medicaments antineoplàstics
Integrines
Mice
0302 clinical medicine
Breast cancer
Ús terapèutic
Antineoplastic agents
lcsh:QH301-705.5
Triple-negative breast cancer
Cells
Cultured
education.field_of_study
lcsh:R5-920
chemoresistance
Drug holiday
Metabolisme
030220 oncology & carcinogenesis
triple-negative breast cancer
Neoplastic Stem Cells
Female
Taxoids
lcsh:Medicine (General)
TNBC
medicine.drug
Population
Antineoplastic Agents
Biology
patient-derived orthoxenografts
Article
Cell Line
Càncer de mama
03 medical and health sciences
Genetics
medicine
Animals
Humans
education
PDX
Resistència als medicaments
Chemotherapy
Taxane
Therapeutic use
Cell Biology
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Metabolism
lcsh:Biology (General)
Drug Resistance
Neoplasm
Cancer research
CD49f tumor-initiating cells
Developmental Biology
Zdroj: Recercat. Dipósit de la Recerca de Catalunya
instname
Stem Cell Reports
Dipòsit Digital de la UB
Universidad de Barcelona
Stem Cell Reports, Vol 8, Iss 5, Pp 1392-1407 (2017)
Popis: Summary 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.
Graphical Abstract
Highlights • PDX models mimic the clinical response to docetaxel in breast cancer patients • Sensitivity to docetaxel can be regained in metastatic resistant TNBC • A tumor-initiating CD49f chemoresistant population is present in TNBC • Docetaxel resistance associates with the expansion of a CD49f+ population in TNBC
To study docetaxel resistance in breast cancer, González-Suárez and colleagues utilize multiple PDX models including sensitive-resistant tumor pairs. The characterization of the tumor-initiating CD49f+ chemoresistant population that expands after acquisition of docetaxel resistance reveals potential biomarkers and novel targets for the treatment of resistant metastatic TNBC disease.
Databáze: OpenAIRE
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