Targeting bcl-2 in cancer: Advances, challenges, and perspectives

Research output: Contribution to journalReview articlepeer-review

210 Scopus citations

Abstract

The major form of cell death in normal as well as malignant cells is apoptosis, which is a programmed process highly regulated by the BCL-2 family of proteins. This includes the antiapop-totic proteins (BCL-2, BCL-XL, MCL-1, BCLW, and BFL-1) and the proapoptotic proteins, which can be divided into two groups: the effectors (BAX, BAK, and BOK) and the BH3-only proteins (BIM, BAD, NOXA, PUMA, BID, BIK, HRK. Notably, the BCL-2 antiapoptotic proteins are often overex-pressed in malignant cells. While this offers survival advantages to malignant cells and strengthens their drug resistance capacity, it also offers opportunities for novel targeted therapies that selectively kill such cells. This review provides a comprehensive overview of the extensive preclinical and clinical studies targeting BCL-2 proteins with various BCL-2 proteins inhibitors with emphasis on venetoclax as a single agent, as well as in combination with other therapeutic agents. This review also discusses recent advances, challenges focusing on drug resistance, and future perspectives for effective targeting the Bcl-2 family of proteins in cancer.

Original languageBritish English
Article number1292
Pages (from-to)1-13
Number of pages13
JournalCancers
Volume13
Issue number6
DOIs
StatePublished - 2 Mar 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • AML
  • BCL-2
  • Cancer
  • CLL
  • Resistance
  • Therapy
  • Venetoclax

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