Microfluidic-Based Dynamic BH3 Profiling

Precision medicine is starting to incorporate functional assays to evaluate anticancer agents on patient-isolated tissues or cells to select the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and has extensively been used to predict treatment efficacy in different types of cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events (‘priming’) and anticipate therapy-induced cell death leading to tumor elimination.

This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, which limits drug screening on patient samples, especially in solid tumors. To solve this problem, researchers have developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. They used microfluidic chips to generate a gradient of BIM BH3 peptide, compared it with the standard flow cytometry-based DBP, and tested different anticancer treatments.

Researchers first examined this new technology’s predictive capacity using gastrointestinal stromal tumor (GIST) cell lines by comparing imatinib-sensitive and resistant cells. They could detect differences in apoptotic priming and anticipate cytotoxicity. They then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use, and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for cancer patients.

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