Overcoming BTK Inhibitor Resistance in Chronic Lymphocytic Leukemia by Targeting PKCβ.

Resistance of chronic lymphocytic leukemia to BTK inhibitors poses a major clinical challenge; however, there is potential to overcome this obstacle by targeting the downstream protein kinase PKCβ using the novel inhibitor MS-553. By inhibiting PKCβ, MS-553 blocks B-cell receptor signaling and WNT/β-catenin and NF-κB functions, thereby inducing apoptosis in BTK inhibitor-resistant cells. See related article by Gordon et al., p. 85.