Role of the HGF/c-MET tyrosine kinase inhibitors in metastasic melanoma

Mol Cancer. 2018 Feb 19;17(1):26. doi: 10.1186/s12943-018-0795-z.

Abstract

Metastatic disease in a cancer patient still remains a therapeutic challenge. Metastatic process involves many steps, during which malignant cells succeed to activate cellular pathways promoting survival in hostile environment, engraftment and growth at the distant site from the primary tumor. Melanoma is known for its high propensity to produce metastases even at the early stages of the disease. Here we summarize the most important molecular mechanisms which were associated with the melanoma metastasis. Then, we specifically focus on the signaling pathway mediated by hepatocyte growth factor (HGF) and its receptor c-Met, which play an important role during physiological processes and were been associated with tumorigenesis. We also focus on the effect of the small molecule inhibitors of the tyrosine kinase domain of the c-Met receptor and its effects on properties of melanoma cell. We summarize recent studies, which involved inhibition of the HGF/c-Met signaling in order to decrease melanoma growth and metastatic capacity.

Keywords: A375 Human malignant melanoma cell line.; C-met receptor; Hepatocyte growth factor; Malignant melanoma; Metastasis; Tyrosine kinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Enzyme Inhibitors / therapeutic use*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Neoplasm Metastasis / drug therapy*
  • Neoplasm Metastasis / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-met / metabolism*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics

Substances

  • Enzyme Inhibitors
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met