PKCβ Inhibitor MS-553 Displays Preclinical Efficacy in Both Treatment-Naïve and BTK Inhibitor–Resistant Chronic Lymphocytic Leukemia

This study identified and characterized PKCβ as a therapeutic target in CLL, including CLL resistant to BTKis. Inhibition of PKCβ suppressed both BCR and Wnt/β-catenin signaling, delayed disease progression in vivo, overcame BTKi resistance mechanisms, and enhanced response to BCL-2 inhibition. See related commentary by Jebaraj and Stilgenbauer, p. 21.