# From basic apoptosis discoveries to advanced selective BCL-2 family inhibitors

Source: https://onco.cc/key-papers/paper-bcl-2-cll-nat-rev-drug-discov-2017/  
OnCo record `paper-bcl-2-cll-nat-rev-drug-discov-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Review on BCL-2 in Chronic lymphocytic leukaemia, in Nature Reviews Drug Discovery (2017), one of the most cited Europe PMC records with BCL-2 in its title.

## Summary

Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-X L dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer. Clinical experience with navitoclax prompted the generation of the highly selective BCL-2 inhibitor venetoclax, which is now approved in the United States for the treatment of patients with chronic lymphocytic leukaemia with 17p deletion who have received at least one prior therapy. Recent advances have also been made in the development of potent and selective inhibitors of BCL-X L and myeloid cell leukaemia 1 (MCL1), which are additional BCL-2 family members with established anti-apoptotic roles in cancer. Here we review the latest progress in direct and selective targeting of BCL-2 family proteins for cancer therapy.

Indexed on Europe PMC as PubMed record 28209992 (DOI 10.1038/nrd.2016.253). Its title names BCL-2 and its text names Chronic lymphocytic leukaemia; PubMed types it as a review (Review). It was matched automatically to the idea "BTK degraders to pre-empt resistance in frontline CLL" and no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Reviews Drug Discovery
- Year: 2017
- DOI: 10.1038/nrd.2016.253
- Authors: Ashkenazi A, Fairbrother WJ, Leverson JD, et al.
- What it means: One of the most cited reviews Europe PMC returns for BCL-2 in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Caveats: Matched by BCL-2 in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.; A review summarises other studies; the primary reports it cites are the evidence.

## Sources

- Nat Rev Drug Discov 2017: https://doi.org/10.1038/nrd.2016.253
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28209992/
- Europe PMC: https://europepmc.org/article/MED/28209992

## Connected records

- journals: [Nature Reviews Drug Discovery](https://onco.cc/journals/nature-reviews-drug-discovery/)
- ideas: [BTK degraders to pre-empt resistance in frontline CLL](https://onco.cc/ideas/idea-btk-degrader-frontline/)

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