ABT‐199 (Venetoclax), a BH3‐mimetic Bcl‐2 inhibitor, does not cause Ca 2+ ‐signalling dysregulation or toxicity in pancreatic acinar cells

Many cancer cells depend on anti-apoptotic B-cell lymphoma 2 (Bcl-2) proteins for their survival. Bcl-2 antagonism through Bcl-2 homology 3 (BH3) mimetics has emerged as a novel anti-cancer therapy. ABT-199 (Venetoclax), a recently developed BH3 mimetic that selectively inhibits Bcl-2, was introduced into the clinic for treatment of relapsed chronic lymphocytic leukaemia. Early generations of Bcl-2 inhibitors evoked sustained Ca 2+ responses in pancreatic acinar cells (PACs) inducing cell death. Therefore, BH3 mimetics could potentially be toxic for the pancreas when used to treat cancer. Although ABT-199 was shown to kill Bcl-2-dependent cancer cells without affecting intracellular Ca 2+ signalling, its effects on PACs have not yet been determined. Hence, it is essential and timely to assess whether this recently approved anti-leukaemic drug might potentially have pancreatotoxic effects.