2026-04-29T06:15:54Zhttps://repisalud.isciii.es/rest/oai/requestoai: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
Repisalud
author
Cazet, Aurélie S
author
Hui, Mun N
author
Elsworth, Benjamin L
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Wu, Sunny Z
author
Roden, Daniel
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Chan, Chia-Ling
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Skhinas, Joanna N
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Collot, Raphaël
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Yang, Jessica
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Harvey, Kate
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Johan, M Zahied
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Cooper, Caroline
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Nair, Radhika
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Herrmann, David
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McFarland, Andrea
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Deng, Niantao
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Ruiz-Borrego, Manuel
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Rojo, Federico
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Trigo, José M
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Bezares, Susana
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Caballero, Rosalía
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Lim, Elgene
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Timpson, Paul
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O'Toole, Sandra
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Watkins, D Neil
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Cox, Thomas R
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Samuel, Michael S
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Martín, Miguel
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Swarbrick, Alexander
2024-02-08T14:41:37Z
2024-02-08T14:41:37Z
2018-07-24
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
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.
eng
Targeting stromal remodeling and cancer stem cell plasticity overcomes chemoresistance in triple negative breast cancer.
research article