High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors.

High-throughput dynamic BH3 profiling may quickly and accurately predict effective therapies in solid tumors. Sci Signal. 2020 Jun 16;13(636): Authors: Bhola PD, Ahmed E, Guerriero JL, Sicinska E, Su E, Lavrova E, Ni J, Chipashvili O, Hagan T, Pioso MS, McQueeney K, Ng K, Aguirre AJ, Cleary JM, Cocozziello D, Sotayo A, Ryan J, Zhao JJ, Letai A 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 vulnerabilit...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research