Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/40149
Title: Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer.
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Issue Date: 2018
Citation: Nat Commun.2018 07;(9)1:2897
Abstract: The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibroblasts (CAFs) to provide a supportive niche for the acquisition of a chemo-resistant, cancer stem cell (CSC) phenotype via FGF5 expression and production of fibrillar collagen. Stromal treatment of patient-derived xenografts with smoothened inhibitors (SMOi) downregulates CSC markers expression and sensitizes tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden. In the phase I clinical trial EDALINE, 3 of 12 patients with metastatic TNBC derived clinical benefit from combination therapy with the SMOi Sonidegib and docetaxel chemotherapy, with one patient experiencing a complete response. These studies identify Hedgehog signaling to CAFs as a novel mediator of CSC plasticity and an exciting new therapeutic target in TNBC.
PMID: 30042390
URI: https://hdl.handle.net/20.500.12530/40149
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. General U. Gregorio Marañón > Artículos

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