Targeting GSK3: Beyond the mitotic spindle?

Abstract

In this issue of Blood, Wu et al1 present preclinical data on the novel therapeutic target GSK3, a pleotropic regulator of signaling pathways involved in cancer. The authors show effective kinase inhibition by the small molecule inhibitor 9-ING-41, leading to mitotic spindle interference, consequent mitotic arrest, and lymphoma-specific cytotoxicity in vitro and in vivo. These data points offer the first mechanistic insight into GSK3-related biology and onco-addiction in non-Hodgkin lymphomas (NHLs) and provide a strong preclinical rationale for a phase 1/2 clinical trial of GSK3 inhibition in relapsed NHL to evaluate safety and efficacy.