Precision medicine is starting to incorporate functional assays to evaluate
anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and 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, that limits
drug screening on patient samples, especially in solid
tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We 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. We first examined this new technology's predictive capacity using
gastrointestinal stromal tumor (GIST) cell lines, by comparing
imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We 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.