The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy

Vogler, Meike; Braun, Yannick; Smith, Victoria M.; Westhoff, Mike‐Andrew; Pereira, Raquel; Pieper, Nadja M.; Anders, Marius; Callens, Manon; Vervliet, Tim; Abbas, Maha; Macip, Salvador; Schmid, Ralf; Bultynck, Geert; Dyer, Martin J.S.

doi:10.1038/s41392-025-02176-0

reviewSignal Transduction and Targeted TherapyMar 21, 2025GOLD OA

The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy

MVMeike Vogler YBYannick Braun VMVictoria M. Smith MWMike‐Andrew Westhoff RPRaquel Pereira

Goethe University Frankfurt · University Hospital Frankfurt · +6 more institutions

PubMed

Indexed incrossrefdoajpubmed

Abstract

Abstract The B cell lymphoma 2 (BCL2) protein family critically controls apoptosis by regulating the release of cytochrome c from mitochondria. In this cutting-edge review, we summarize the basic biology regulating the BCL2 family including canonical and non-canonical functions, and highlight milestones from basic research to clinical applications in cancer and other pathophysiological conditions. We review laboratory and clinical development of BH3-mimetics as well as more recent approaches including proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) and tools targeting the BH4 domain of BCL2. The first BCL2-selective BH3-mimetic, venetoclax, showed remarkable efficacy with manageable…

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249

total citations

FWCI: 152.82
Percentile: 100%
References: 558

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Authors

14

Topics & keywords

Topics

Keywords

MCL1
Venetoclax
Cancer
Computational biology
Medicine
Cancer research
Bioinformatics
Biology

UN Sustainable Development Goals

Good health and well-being

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