Fig. 6: Drug-induced priming increases chemosensitivity resulting in apoptosis.

Mitochondrial outer membrane permeabilization (MOMP) is a switch-like event regulated by the BCL-2 family of proteins. One can imagine MOMP like a cliff and proximity to the cliffs edge has physiological consequences such as commitment to cell death following a toxic perturbation. We consider cells that are relatively close to the cliff’s edge to be relatively “primed” for apoptosis, whereas those relatively far from the cliff’s edge to be relatively “unprimed” In comparison. A When an unprimed cancer cell receives a proapoptotic signal from a chemotherapy agent, it may move a small bit closer to the edge but is not compelled to commit to apoptosis. B A targeted agent, identified by DBP, that primes the cancer cell, pushes it closer to the cliffs edge and therefore lowering the apoptotic threshold. C Drug-induced priming lowers the apoptotic threshold, so the cell is more sensitive to the chemotherapy agent resulting in apoptosis. The key will be to identify the right targeted agent that primes the tumor cell for that patient and combine it with chemotherapy to increase chemosensitivity. Created with BioRender.com.