Melanoma is the leading cause of death due to cutaneous malignancy and its incidence is on the rise. Several signaling pathways, including receptor tyrosine kinases, have been recognized to have an etiopathogenetic role in the development and progression of precursor melanocytic lesions and malignant melanoma. Among those, the hepatocyte growth factor/MET (HGF/MET) axis is emerging as a critical player not only in the tumor itself but also in the immune microenvironment in which the tumor grows and advances in its development. Moreover, the activation of this pathway has emerged as a paradigm of tumor resistance to modern targeted therapies, and the assessment of its expression in patients' samples may be a valuable biomarker of tumor progression and response to targeted therapy. Here we summarize our current understanding of this important receptor tyrosine kinase in normal melanocyte proliferation/motility, in tumor progression and metastasis, its genetic alterations in certain subtype of melanocytic lesions, and how its pathway has been explored for the development of selective inhibitors.
Bibliographical noteFunding Information:
Supported by start-up funds from the Department of Laboratory Medicine and Pathology/ Masonic Cancer Center, University of Minnesota (A.G.).
© 2019 American Society for Investigative Pathology
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