Figure 4.
Scheme for the dynamic BH3 profiling of primary clinical samples. Tumor cells are isolated from either a solid tumor biopsy or blood. Cells are treated with an anticancer agent such as chemotherapy, targeted therapy, or a BH3 mimetic, followed by the addition of BH3 peptides. Mitochondrial depolarization (cytochrome c release) on tumor cells is analyzed by flow cytometry or microscopy. The percentage of change in priming is determined by comparing treated versus control cells, and this parameter predicts response to the agent. By using different BH3 peptides, BH3 profiling can predict response to treatment (using the BIM peptide) or changes in antiapoptotic dependencies (using specific BH3 peptides such as BAD, HRK, or NOXA/MCL1), which indicate potential combination therapies with BH3 mimetics. The overall time from biopsy to results is approximately 24 hours. Adapted from ref. 11 and used under a CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).