Statins in combination with Ibrutinib bypasses resistance to Ibrutinib in mantle cell lymphoma

Abstract

Objective: In this study, we report that a novel combination therapy of different statins with Ibrutinib can overcome such resistance. Methods: For this, we generated a cell line model, exhibiting resistance to Ibrutinib, by repeated exposure of mantle cell lymphoma cell line to Ibrutinib. Apoptosis was assessed by the extent of phosphatidylserine externalisation. Results: Our results indicated that resistance to Ibrutinib could be overcome by targeting a key enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the cholesterogenesis pathway. Conclusion: Reusing different statins in combination with Ibrutinib could improve therapy and enhance sensitivity to Ibrutinib mediated apoptosis.