2026-04-29T06:15:45Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/176142024-09-21T18:33:19Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16978

00925njm 22002777a 4500 dc Cazet, Aurélie S author Hui, Mun N author Elsworth, Benjamin L author Wu, Sunny Z author Roden, Daniel author Chan, Chia-Ling author Skhinas, Joanna N author Collot, Raphaël author Yang, Jessica author Harvey, Kate author Johan, M Zahied author Cooper, Caroline author Nair, Radhika author Herrmann, David author McFarland, Andrea author Deng, Niantao author Ruiz-Borrego, Manuel author Rojo, Federico author Trigo, José M author Bezares, Susana author Caballero, Rosalía author Lim, Elgene author Timpson, Paul author O'Toole, Sandra author Watkins, D Neil author Cox, Thomas R author Samuel, Michael S author Martín, Miguel author Swarbrick, Alexander author 2018-07-24 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. http://hdl.handle.net/10668/12750 http://hdl.handle.net/20.500.12105/17614 30042390 10.1038/s41467-018-05220-6 2041-1723 Nature communications Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer.