New insights into the roles of antiapoptotic members of the Bcl-2 family in melanoma progression and therapy

Drug Discov Today. 2021 May;26(5):1126-1135. doi: 10.1016/j.drudis.2021.01.027. Epub 2021 Feb 2.

Abstract

Prosurvival and antiapoptotic B cell lymphoma-2 (Bcl-2) family proteins are often overexpressed in cutaneous melanoma, one of the most aggressive types of human cancer. They are also implicated in resistance to therapy and participate in melanoma progression by regulating various processes, including cell proliferation, migration, invasion, and crosstalk with the tumor microenvironment. In this review, we summarize recent findings related to prosurvival members of the Bcl-2 family beyond their canonical functions in the apoptotic pathway, mainly focusing on their potential roles as diagnostic and prognostic biomarkers in cutaneous melanoma. We also provide an overview of different approaches used to inhibit Bcl-2 proteins in preclinical and clinical studies, which are mainly based on the inhibition of protein expression or the disruption of their antiapoptotic functions.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Biomarkers, Tumor / metabolism
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Humans
  • Melanoma / diagnosis
  • Melanoma / pathology*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / pathology*
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-bcl-2