Cited by 752Cell death mechanisms and regulationCancer-related Molecular PathwaysClusterin in disease pathology

Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies

Delbridge, Alex R. D., Grabow, Stephanie, Strasser, Andreas, Vaux, David L.·2016·Nature Reviews Cancer

Abstract

The 'hallmarks of cancer' are generally accepted as a set of genetic and epigenetic alterations that a normal cell must accrue to transform into a fully malignant cancer. It follows that therapies designed to counter these alterations might be effective as anti-cancer strategies. Over the past 30 years, research on the BCL-2-regulated apoptotic pathway has led to the development of small-molecule compounds, known as 'BH3-mimetics', that bind to pro-survival BCL-2 proteins to directly activate apoptosis of malignant cells. This Timeline article focuses on the discovery and study of BCL-2, the wider BCL-2 protein family and, specifically, its roles in cancer development and therapy.

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Crossref · 10.1038/nrc.2015.17

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196 of 196 references verified0 citation errors · 0 not checkable

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  • In response to apoptotic stimuli, MOMP is mediated by BAX and/or BAK.

    “In response to apoptotic stimuli, MOMP is mediated by BCL2 associated X, apoptosis regulator (BAX), and/or BCL2 antagonist/killer 1 (BAK1; best known as BAK), both of which contain four BH domains and a conserved transmembrane domain [44–46].”
  • MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space, including cytochrome c (CYCS) and SMAC.

    “MOMP directly promotes the cytosolic release of apoptogenic factors that normally reside in the mitochondrial intermembrane space [40, 44, 156]. These mitochondrial proteins include (but are not limited to) cytochrome c, somatic (CYCS), which usually operates as an electron shuttle in the mitochondrial respiratory chain [157–160], and diablo IAP-binding mitochondrial protein (DIABLO; also known as”
  • Overexpression of drug resistance-associated genes, such as P-gp and Bcl-2, is one of the most consistent alterations in multidrug resistant cells.

    “Overexpression of drug resistance-associated genes, such as P-gp and Bcl-2, is one of the most consistent alterations in multidrug resistant cells [131–134].”

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Authors
Delbridge, A. R. D., Grabow, S., Strasser, A., & Vaux, D. L.
Affiliations
The University of Melbourne (AU)
Corresponding author
  • Strasser, Andreas
  • Vaux, David L.
Venue
Nature Reviews Cancer
Published
2016-01-29
Volume
16
Issue
2
Pages
99-109
ISSN
  • 1474-175X (ISSN-L)
  • 1474-1768
OpenAlex
W2252711380
Cited by
752
References
196
Citations by year
2026: 36 · 2025: 42 · 2024: 65 · 2023: 75 · 2022: 75 · 2021: 100 · 2020: 91 · 2019: 70 · 2018: 78 · 2017: 92 · 2016: 27
FWCI
8.05
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Cancer (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Oncology › Clusterin in disease pathology
Keywords
Bcl-2, Bcl-2 family proteins, apoptosis, BH3 mimetics, cancer therapy, cancer hallmarks
MeSH terms
Animals, Biphenyl Compounds, Multigene Family, Humans, Neoplasms, Nitrophenols, Piperazines, Sulfonamides, Gene Expression Regulation, Neoplastic, Cell Death, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Genes, bcl-2, Mitochondrial Membrane Transport Proteins, bcl-2-Associated X Protein, Mice, Molecular Targeted Therapy

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