ArticleCell death & disease2012
Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B.
Article in Cell death & disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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
51 citing papers in PubMed, 85 citations in OpenAlex.
- A phase I/II study of the pan Bcl-2 inhibitor obatoclax mesylate plus bortezomib for relapsed or refractory mantle cell lymphoma.Leukemia & lymphoma · 2014Trial
- Trial
- BCL2 inhibition in acute and chronic pancreatitis - is there a therapeutic perspective?Cell death discovery · 2026Review
- Discovery of Dual BCL-xL/BCL-w Degraders by Exploiting the Bis(sulfonyl)benzene Ring of ABT-263 as a Linkage Vector.Journal of medicinal chemistry · 2025Article
- VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.Nature communications · 2025Article
- Inhibition of bromodomain and extra-terminal proteins targets constitutively active NFκB and STAT signaling in lymphoma and influences the expression of the antiapoptotic proteins BCL2A1 and c-MYC.Cell communication and signaling : CCS · 2024Article
- Bcl-B: an "unknown" protein of the Bcl-2 family.Biology direct · 2023Review
- Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol.Cell death and differentiation · 2022Article
- Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death.Oncotarget · 2021Article
- BCL2L10 Is Overexpressed in Melanoma Downstream of STAT3 and Promotes Cisplatin and ABT-737 Resistance.Cancers · 2020Article
- Article
- BCL-w: apoptotic and non-apoptotic role in health and disease.Cell death & disease · 2020Review
- NOXA-dependent contextual synthetic lethality of BCL-XL inhibition and "osmotic reprogramming" in colorectal cancer.Cell death & disease · 2020Article
- Nanoparticle-Mediated Co-Delivery of Notch-1 Antibodies and ABT-737 as a Potent Treatment Strategy for Triple-Negative Breast Cancer.ACS nano · 2020Article
- Article
- Transmembrane protein GRINA modulates aerobic glycolysis and promotes tumor progression in gastric cancer.Journal of experimental & clinical cancer research : CR · 2018Article
- Targeting mitochondria in cancer: current concepts and immunotherapy approaches.Translational research : the journal of laboratory and clinical medicine · 2018Review
- NOXA genetic amplification or pharmacologic induction primes lymphoma cells to BCL2 inhibitor-induced cell death.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line.Annals of surgical treatment and research · 2018Article
- Combined HAT/EZH2 modulation leads to cancer-selective cell death.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The novel anticancer drug ABT-737 is a Bcl-2 Homology 3 (BH3)-mimetic that induces apoptosis by inhibiting pro-survival Bcl-2 proteins. ABT-737 binds with equal affinity to Bcl-2, Bcl-xL and Bcl-w in vitro and is expected to overrule apoptosis resistance mediated by these Bcl-2 proteins in equal measure. We have profiled ABT-737 specificity for all six pro-survival Bcl-2 proteins, in p53 wild-type or p53-mutant human T-leukemic cells. Bcl-B was untargeted, like Bfl-1 and Mcl-1, in accord with their low affinity for ABT-737 in vitro. However, Bcl-2 proved a better ABT-737 target than Bcl-xL and Bcl-w. This was reflected in differential apoptosis-sensitivity to ABT-737 alone, or combined with etoposide. ABT-737 was not equally effective in displacing BH3-only proteins or Bax from Bcl-2, as compared with Bcl-xL or Bcl-w, offering an explanation for the differential ABT-737 sensitivity of tumor cells overexpressing these proteins. Inducible expression demonstrated that BH3-only proteins Noxa, but not Bim, Puma or truncated Bid could overrule ABT-737 resistance conferred by Bcl-B, Bfl-1 or Mcl-1. These data identify Bcl-B, Bfl-1 and Mcl-1, but also Bcl-xL and Bcl-w as potential mediators of ABT-737 resistance and indicate that target proteins can be differentially sensitive to BH3-mimetics, depending on the pro-apoptotic Bcl-2 proteins they are complexed with.
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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 OpenQuestion graph.