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Highly Accessed Review

The Hedgehog signalling pathway in breast development, carcinogenesis and cancer therapy

Mun Hui1, Aurélie Cazet1, Radhika Nair1, D Neil Watkins2, Sandra A O'Toole1345 and Alexander Swarbrick13*

Author Affiliations

1 The Kinghorn Cancer Center and Cancer Res Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia

2 Monash Institute of Medical Research, Monash University, Clayton, Victoria 3168, Australia

3 St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, NSW 2052, Australia

4 Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia

5 Sydney Medical School, University of Sydney, NSW 2006, Australia

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Breast Cancer Research 2013, 15:203  doi:10.1186/bcr3401

Published: 28 March 2013

Abstract

Despite the progress achieved in breast cancer screening and therapeutic innovations, the basal-like subtype of breast cancer (BLBC) still represents a particular clinical challenge. In order to make an impact on survival in this type of aggressive breast cancer, new targeted therapeutic agents are urgently needed. Aberrant activation of the Hedgehog (Hh) signalling pathway has been unambiguously tied to cancer development and progression in a variety of solid malignancies, and the recent approval of vismodegib, an orally bioavailable small-molecule inhibitor of Smoothened, validates Hh signalling as a valuable therapeutic target. A number of recent publications have highlighted a role for Hh signalling in breast cancer models and clinical specimens. Interestingly, Hh ligand overexpression is associated with the BLBC phenotype and a poor outcome in terms of metastasis and breast cancer-related death. In this review, we provide a comprehensive overview of the canonical Hh signalling pathway in mammals, highlight its roles in mammary gland development and breast carcinogenesis and discuss its potential therapeutic value in BLBC.