RAC1 Activation as a Potential Therapeutic Option in Metastatic Cutaneous Melanoma

Biomolecules. 2021 Oct 20;11(11):1554. doi: 10.3390/biom11111554.

Abstract

Metastasis is a complex process by which cancer cells escape from the primary tumor to colonize distant organs. RAC1 is a member of the RHO family of small guanosine triphosphatases that plays an important role in cancer migration, invasion, angiogenesis and metastasis. RAC1 activation has been related to most cancers, such as cutaneous melanoma, breast, lung, and pancreatic cancer. RAC1P29S driver mutation appears in a significant number of cutaneous melanoma cases. Likewise, RAC1 is overexpressed or hyperactivated via signaling through oncogenic cell surface receptors. Thus, targeting RAC1 represents a promising strategy for cutaneous melanoma therapy, as well as for inhibition of other signaling activation that promotes resistance to targeted therapies. In this review, we focus on the role of RAC1 in metastatic cutaneous melanoma emphasizing the anti-metastatic potential of RAC1- targeting drugs.

Keywords: RAC1; cutaneous melanoma; invasion; metastasis; therapy resistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • Melanoma, Cutaneous Malignant
  • Neoplasm Metastasis
  • Signal Transduction / drug effects
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / metabolism
  • Skin Neoplasms* / pathology
  • rac1 GTP-Binding Protein* / genetics
  • rac1 GTP-Binding Protein* / metabolism

Substances

  • rac1 GTP-Binding Protein
  • RAC1 protein, human
  • Antineoplastic Agents