ArticleNature communications2023
Dynamic BH3 profiling identifies pro-apoptotic drug combinations for the treatment of malignant pleural mesothelioma.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- What does not kill you makes you Weaker!Cell death and differentiation · 2026Article
- Pseudo-senescence induced by palbociclib does not sensitise pleural mesothelioma cells to combinations with senolytics.Cell death & disease · 2026Article
- Therapeutic potential of BH3-mimetics and NK cell-mediated immunotherapy in T-ALL.Cell death & disease · 2026Article
- Experimentally calibrated multiscale model predicts schedule dependent drug combination effects.NPJ systems biology and applications · 2026Article
- Informing development of brain cancer therapies within "preclinical trials" using ex vivo patient tumors.Advanced drug delivery reviews · 2026Review
- Co-Targeting BCL-xL with MCL-1 Induces Lethal Mitochondrial Dysfunction in Diffuse Mesothelioma.Molecular cancer therapeutics · 2025Article
- Molecular mechanisms underlying HRK interaction with BCL-XL and BCL-2 reveal specificity determinants for BH3 mimetics.iScience · 2025Article
- Re-appraising assays on permeabilized blood cancer cells testing venetoclax or other BH3 mimetic agents selectively targeting pro-survival BCL2 proteins.Cell death and differentiation · 2025Article
- Comparing functional and genomic-based precision medicine in blood cancer patients.HemaSphere · 2025Article
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- A Bayesian active learning platform for scalable combination drug screens.Nature communications · 2025Article
- Development of a robust BH3 drug toolkit for precision medicine in hematologic malignancies.Theranostics · 2025Article
- Mitochondrial priming in therapy-induced senescence: implications for CAR-T/NK immunosenolytic therapy.Frontiers in immunology · 2025Review
- Full-course NIR-II imaging-navigated fractionated photodynamic therapy of bladder tumours with X-ray-activated nanotransducers.Nature communications · 2024Article
- Venetoclax Combined with Intensive Chemotherapy: A New Hope for Refractory and/or Relapsed Acute Myeloid Leukemia?Journal of clinical medicine · 2024Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Malignant pleural mesothelioma (MPM) has relatively ineffective first/second-line therapy for advanced disease and only 18% five-year survival for early disease. Drug-induced mitochondrial priming measured by dynamic BH3 profiling identifies efficacious drugs in multiple disease settings. We use high throughput dynamic BH3 profiling (HTDBP) to identify drug combinations that prime primary MPM cells derived from patient tumors, which also prime patient derived xenograft (PDX) models. A navitoclax (BCL-xL/BCL-2/BCL-w antagonist) and AZD8055 (mTORC1/2 inhibitor) combination demonstrates efficacy in vivo in an MPM PDX model, validating HTDBP as an approach to identify efficacious drug combinations. Mechanistic investigation reveals AZD8055 treatment decreases MCL-1 protein levels, increases BIM protein levels, and increases MPM mitochondrial dependence on BCL-xL, which is exploited by navitoclax. Navitoclax treatment increases dependency on MCL-1 and increases BIM protein levels. These findings demonstrate that HTDBP can be used as a functional precision medicine tool to rationally construct combination drug regimens in MPM and other cancers.
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