ArticleACS pharmacology & translational science2025
Understanding the Functional Dependence and Inhibition of the Bcl‑2 Pro-Survival Proteins in a Wide Spectrum of Cancers toward Precision Medicine.
Article in ACS pharmacology & translational science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Engineered Allosteric RNA Editors Enable Compact, Stimulus-Responsive Post-Transcriptional Circuits.bioRxiv : the preprint server for biology · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
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Authors and funding
16 authors.
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Abstract
Introducing and integrating functional assays into clinical cancer care can further enhance the effectiveness of precision cancer medicine. Bcl-2 pro-survival proteins have emerged as promising targets across various cancers, with Venetoclax, a highly selective Bcl-2 inhibitor, being the first approved drug of this category. This study aims to explore BH3 profiling as a functional diagnostic to distinguish pro-survival dependence in a variety of human cancers to identify antiapoptotic Bcl-2 family protein dependencies and sensitivity to BH3 mimetics. The obtained results demonstrate that, in general, hematological cancer cell lines are sensitive to Bcl-2 or Mcl-1 inhibitors. Notably, certain lymphoma subtypes of B-cell and T-cell origin show preferential dependence on Bcl-2 and Mcl-1, respectively. These conclusions were supported and enhanced by follow-up studies of primary patient-derived samples. Immunohistochemistry of patient specimens supported the identified overexpression and functional involvement of Bfl-1 in T-cell lymphomas, highlighting a new potential precision therapy opportunity. Functional profiling of various solid tumor cell lines, including ovarian cancer PDX models, revealed that most solid tumors have a dependence on a combination of Bcl-2 family antiapoptotic proteins. Treatment with a combination of Bcl-xL and Mcl-1 inhibitors induced significant apoptosis in a majority of the tested solid tumor cell lines. The results of this study reveal a functional dependence on Bcl-2 antiapoptotic proteins in various cancers and offer more tailored strategies for utilizing BH3 mimetics in precision cancer therapy.
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