ReviewCell death and differentiation2025
The BCL-2 protein family: from discovery to drug development.
Review in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- The potential role of miR-34a and miR-34c in the regulation of pediatric high-grade glioma 4 aggressiveness.Pediatric research · 2026Article
- Comparative insights into the apoptosome, inflammasomes and PIDDosome.Nature reviews. Immunology · 2026Review
- BCLXSignal transduction and targeted therapy · 2026Article
- Proteolysis Targeting Chimera (PROTAC) Linkerology Enhances the CDK-Degradation Selectivity Profile of a Multi-CDK Inhibitor: Discovery of Potent, Anti-Leukemic CDK9 Degraders.ACS pharmacology & translational science · 2026Article
- BCL-2 inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques.Nature microbiology · 2026Article
- Rewiring of the Apoptotic Rheostat in HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma.Cancers · 2026Review
- Targeted co-delivery of docetaxel and plumbagin via oxidative priming enhances chemoradiotherapy in non-small cell lung cancer.Materials today. Bio · 2026Article
- TMBIM6: at the intersection between proteostasis dysregulation and Parkinson's disease.Cell death and differentiation · 2026Article
- Diagnosis-Driven Targeted Therapy in Acute Myeloid Leukemia: Clinical Integration of Tyrosine Kinase, BCL-2, and CD33-Directed Strategies with Midostaurin, Venetoclax, and Gemtuzumab Ozogamicin.Journal of clinical medicine · 2026Review
- Apoptosis signaling and cancer targeted therapy: from bench to bespoke.Translational cancer research · 2026Review
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Benzimidazole derivatives as dual EGFR and BRAFRSC advances · 2026Article
- The evolving global landscape of first-in-class oncology drug innovation.Signal transduction and targeted therapy · 2026Review
- Crystal structure of Bcl-2 from lymphocystis disease virus 2 in complex with the BH3 domain of zebrafish BaxA.Journal of microbiology (Seoul, Korea) · 2026Article
- A century of cell death research.Journal of cell science · 2026Review
- Liraglutide reduces the apoptosis of feeding and appetite-suppressing neurons in the hypothalamus of obese rats association with the PI3K/AKT/Foxo1 pathway.Experimental brain research · 2026Article
- Design, synthesis and antiproliferative, apoptotic, and immunomodulatory properties of new heteroaryl pyridine-linked 1,2,4-oxadiazoles as prospective dual EGFR/BRAFRSC advances · 2026Article
- Protein structural dynamics in covalent drug design: insights from irreversible and reversible covalent inhibitors.RSC chemical biology · 2026Review
- Prox1 maintains taste bud structure via inhibition of apoptosis.Cell and tissue research · 2026Article
- Identification of key genes potentially associated with bladder cancer development by common plasticizers: an integrated transcriptomics and network toxicology study.Frontiers in oncology · 2026Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The landmark discovery of the BCL-2 gene and then its function marked the identification of inhibition of apoptotic cell death as a crucial novel mechanism driving cancer development and launched the quest to discover the molecular control of apoptosis. This work culminated in the generation of specific inhibitors that are now in clinical use, saving and improving tens of thousands of lives annually. Here, some of the original players of this story, describe the sequence of critical discoveries. The t(14;18) chromosomal translocation, frequently observed in follicular lymphoma, allowed the identification and the cloning of a novel oncogene (BCL-2) juxtaposed to the immunoglobulin heavy chain gene locus (IgH). Of note, BCL-2 acted in a distinct manner as compared to then already known oncogenic proteins like ABL and c-MYC. BCL-2 did not promote cell proliferation but inhibited cell death, as originally shown in growth factor dependent haematopoietic progenitor cell lines (e.g., FDC-P1) and in Eμ-Myc/Eμ-Bcl-2 double transgenic mice. Following a rapid expansion of the BCL-2 protein family, the Abbott Laboratories solved the first structure of BCL-XL and subsequently the BCL-XL/BAK peptide complex, opening the way to understanding the structures of other BCL-2 family members and, finally, to the generation of inhibitors of the different pro-survival BCL-2 proteins, thanks to the efforts of Servier/Norvartis, Genentech/WEHI, AbbVie, Amgen, Prelude and Gilead. Although the BCL-2 inhibitor Venetoclax is in clinical use and inhibitors of BCL-XL and MCL-1 are undergoing clinical trials, several questions remain on whether therapeutic windows can be achieved and what other agents should be used in combination with BH3 mimetics to achieve optimal therapeutic impact for cancer therapy. Finally, the control of the expression of BH3-only proteins and pro-survival BCL-2 family members needs to be better understood as this may identify novel targets for cancer therapy. This story is still not concluded!
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.