RAC1 as a Therapeutic Target in Malignant Melanoma

Trends Cancer. 2020 Jun;6(6):478-488. doi: 10.1016/j.trecan.2020.02.021. Epub 2020 Mar 18.

Abstract

Small GTPases of the RAS and RHO families are related signaling proteins that, when activated by growth factors or by mutation, drive oncogenic processes. While activating mutations in KRAS, NRAS, and HRAS genes have long been recognized and occur in many types of cancer, similar mutations in RHO family genes, such as RAC1 and RHOA, have only recently been detected as the result of extensive cancer genome-sequencing efforts and are linked to a restricted set of malignancies. In this review, we focus on the role of RAC1 signaling in malignant melanoma, emphasizing recent advances that describe how this oncoprotein alters melanocyte proliferation and motility and how these findings might lead to new therapeutics in RAC1-mutant tumors.

Keywords: cancer therapeutics; driver mutations; effectors; fast-cycling; malignant melanoma; signal transduction; small GTPases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Line, Tumor
  • Disease Models, Animal
  • Drug Synergism
  • Gain of Function Mutation
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / genetics
  • Melanoma / pathology
  • Phosphatidylinositol 3-Kinase
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Serum Response Factor / antagonists & inhibitors
  • Serum Response Factor / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • p21-Activated Kinases / antagonists & inhibitors
  • p21-Activated Kinases / metabolism
  • rac1 GTP-Binding Protein / antagonists & inhibitors*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism

Substances

  • MRTFA protein, human
  • MRTFB protein, human
  • Protein Kinase Inhibitors
  • RAC1 protein, human
  • SRF protein, human
  • Serum Response Factor
  • Trans-Activators
  • Transcription Factors
  • Phosphatidylinositol 3-Kinase
  • p21-Activated Kinases
  • rac1 GTP-Binding Protein