The HGF-cMET signaling pathway in conferring stromal-induced BRAF-inhibitor resistance in melanoma

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Genetic heterogeneity in melanoma is well established. Given this, as well as the complexity of mechanisms involved in cancer in vivo, a more complete understanding of the development of resistance requires a closer look at the tumor ecosystem, including the microenvironment. Echoing this more comprehensive approach, a number of recent studies on BRAF-inhibitor resistance have brought our attention back to the tumor microenvironment, particularly through a focus on HGF-cMET signaling – a known means of stromal–parenchymal communication. Our review focuses on the results of these recent investigations, and through a review of relevant HGF-cMET past literature looks to provide a context by which to better understand the role of stromal–parenchymal signaling in BRAF resistance/melanoma progression.

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