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Breast Cancer Res. 2015 Apr 8;17:52. doi: 10.1186/s13058-015-0547-6.

The clinical and functional significance of c-Met in breast cancer: a review.

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Department of Cellular Pathology, St George's Healthcare NHS Trust, Blackshaw Road, Tooting, London, SW17 0QT, UK.
Centre for Tumour Biology, Barts Cancer Institute, Charterhouse Square, London, EC1M 6BQ, UK.
Centre for Tumour Biology, Barts Cancer Institute, Charterhouse Square, London, EC1M 6BQ, UK.


c-Met is a receptor tyrosine kinase that upon binding of its ligand, hepatocyte growth factor (HGF), activates downstream pathways with diverse cellular functions that are important in organ development and cancer progression. Anomalous c-Met signalling has been described in a variety of cancer types, and the receptor is regarded as a novel therapeutic target. In breast cancer there is a need to develop new treatments, particularly for the aggressive subtypes such as triple-negative and basal-like cancer, which currently lack targeted therapy. Over the last two decades, much has been learnt about the functional role of c-Met signalling in different models of breast development and cancer. This work has been complemented by clinical studies, establishing the prognostic significance of c-Met in tissue samples of breast cancer. While the clinical trials of anti-c-Met therapy in advanced breast cancer progress, there is a need to review the existing evidence so that the potential of these treatments can be better appreciated. The aim of this article is to examine the role of HGF/c-Met signalling in in vitro and in vivo models of breast cancer, to describe the mechanisms of aberrant c-Met signalling in human tissues, and to give a brief overview of the anti-c-Met therapies currently being evaluated in breast cancer patients. We will show that the HGF/c-Met pathway is associated with breast cancer progression and suggest that there is a firm basis for continued development of anti-c-Met treatment, particularly for patients with basal-like and triple-negative breast cancer.

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