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Role of Hedgehog Signaling in Breast Cancer: Pathogenesis and Therapeutics

School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
Leeds Institute of Medical Research, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
Laboratorio de Transducción de señales y cáncer, Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, Argentina
Authors to whom correspondence should be addressed.
Cells 2019, 8(4), 375;
Received: 2 April 2019 / Revised: 22 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)
PDF [672 KB, uploaded 25 April 2019]


Breast cancer (BC) is the leading cause of cancer-related mortality in women, only followed by lung cancer. Given the importance of BC in public health, it is essential to identify biomarkers to predict prognosis, predetermine drug resistance and provide treatment guidelines that include personalized targeted therapies. The Hedgehog (Hh) signaling pathway plays an essential role in embryonic development, tissue regeneration, and stem cell renewal. Several lines of evidence endorse the important role of canonical and non-canonical Hh signaling in BC. In this comprehensive review we discuss the role of Hh signaling in breast development and homeostasis and its contribution to tumorigenesis and progression of different subtypes of BC. We also examine the efficacy of agents targeting different components of the Hh pathway both in preclinical models and in clinical trials. The contribution of the Hh pathway in BC tumorigenesis and progression, its prognostic role, and its value as a therapeutic target vary according to the molecular, clinical, and histopathological characteristics of the BC patients. The evidence presented here highlights the relevance of the Hh signaling in BC, and suggest that this pathway is key for BC progression and metastasis. View Full-Text
Keywords: hedgehog; breast cancer; clinical trial; sonic; Patched-1; Smoothened; glioma-associated oncogene; TNBC; therapeutics hedgehog; breast cancer; clinical trial; sonic; Patched-1; Smoothened; glioma-associated oncogene; TNBC; therapeutics

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Riobo-Del Galdo, N.A.; Lara Montero, Á.; Wertheimer, E.V. Role of Hedgehog Signaling in Breast Cancer: Pathogenesis and Therapeutics. Cells 2019, 8, 375.

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