ArticleScience signaling2020
High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors.
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed.
- Integration and validation of complementary ex vivo assays for functional precision oncology.NPJ precision oncology · 2026Article
- Experimentally calibrated multiscale model predicts schedule dependent drug combination effects.NPJ systems biology and applications · 2026Article
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Apoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies.Cell death and differentiation · 2025Article
- Worldwide Innovative Network (WIN) Consortium in Personalized Cancer Medicine: Bringing next-generation precision oncology to patients.Oncotarget · 2025Article
- Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.Cell death discovery · 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
- Approaches to modeling cancer metastasis: from bench to bedside.Frontiers in oncology · 2025Review
- BH3 Mimetics Augment Cytotoxic T Cell Killing of Acute Myeloid Leukemia via Mitochondrial Apoptotic Mechanism.Research square · 2024Article
- Epigenetic and Oncogenic Inhibitors Cooperatively Drive Differentiation and Kill KRAS-Mutant Colorectal Cancers.Cancer discovery · 2024Article
- Integrated molecular and functional characterization of the intrinsic apoptotic machinery identifies therapeutic vulnerabilities in glioma.Nature communications · 2024Article
- Metastatic progression of breast cancer along with decreased mitochondrial cell death priming of breast cancer cells: a case report.Oxford medical case reports · 2024Article
- Fatty acid synthase (FASN) signalome: A molecular guide for precision oncology.Molecular oncology · 2024Article
- Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches.Frontiers in oncology · 2024Review
- Review
- Sequential apoptotic and multiplexed proteomic evaluation of single cancer cells.Science advances · 2023Article
- Drug screening at single-organoid resolution via bioprinting and interferometry.Nature communications · 2023Article
- Precision Hydrogels for the Study of Cancer Cell Mechanobiology.Advanced healthcare materials · 2023Review
- Non-lethal outcomes of engaging regulated cell death pathways in cancer.Nature cancer · 2023Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Despite decades of effort, the sensitivity of patient tumors to individual drugs is often not predictable on the basis of molecular markers alone. Therefore, unbiased, high-throughput approaches to match patient tumors to effective drugs, without requiring a priori molecular hypotheses, are critically needed. Here, we improved upon a method that we previously reported and developed called high-throughput dynamic BH3 profiling (HT-DBP). HT-DBP is a microscopy-based, single-cell resolution assay that enables chemical screens of hundreds to thousands of candidate drugs on freshly isolated tumor cells. The method identifies chemical inducers of mitochondrial apoptotic signaling, a mechanism of cell death. HT-DBP requires only 24 hours of ex vivo culture, which enables a more immediate study of fresh primary tumor cells and minimizes adaptive changes that occur with prolonged ex vivo culture. Effective compounds identified by HT-DBP induced tumor regression in genetically engineered and patient-derived xenograft (PDX) models of breast cancer. We additionally found that chemical vulnerabilities changed as cancer cells expanded ex vivo. Furthermore, using PDX models of colon cancer and resected tumors from colon cancer patients, our data demonstrated that HT-DBP could be used to generate personalized pharmacotypes. Thus, HT-DBP appears to be an ex vivo functional method with sufficient scale to simultaneously function as a companion diagnostic, therapeutic personalization, and discovery tool.
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