HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence

Oncogene. 2021 Jul;40(28):4625-4651. doi: 10.1038/s41388-021-01863-w. Epub 2021 Jun 18.

Abstract

This review provides a comprehensive landscape of HGF/c-MET (hepatocyte growth factor (HGF) /mesenchymal-epithelial transition factor (c-MET)) signaling pathway in cancers. First, we generalize the compelling influence of HGF/c-MET pathway on multiple cellular processes. Then, we present the genomic characterization of HGF/c-MET pathway in carcinogenesis. Furthermore, we extensively illustrate the malignant biological behaviors of HGF/c-MET pathway in cancers, in which hyperactive HGF/c-MET signaling is considered as a hallmark. In addition, we investigate the current clinical trials of HGF/c-MET-targeted therapy in cancers. We find that although HGF/c-MET-targeted therapy has led to breakthroughs in certain cancers, monotherapy of targeting HGF/c-MET has failed to demonstrate significant clinical efficacy in most cancers. With the advantage of the combinations of HGF/c-MET-targeted therapy, the exploration of more options of combinational targeted therapy in cancers may be the major challenge in the future.

Publication types

  • Review

MeSH terms

  • Animals
  • Hepatocyte Growth Factor* / genetics
  • Hepatocyte Growth Factor* / metabolism
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Proto-Oncogene Proteins c-met* / genetics
  • Proto-Oncogene Proteins c-met* / metabolism
  • Signal Transduction*

Substances

  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • HGF protein, human
  • MET protein, human