Drug Repurposing Screen Identifies Pimozide as a ROS-Inducing Therapy With Anti-Tumor Efficacy in HNSCC PDX Models.

ABSTRACT: Redox regulation is a key mechanism supporting tumor survival and an attractive therapeutic target. In this study, we screened 1161 FDA-approved compounds to identify agents that induce reactive oxygen species (ROS) accumulation in head and neck squamous cell carcinoma (HNSCC) cells. Pimozide, a dopamine D2 receptor antagonist, emerged as the most potent ROS inducer. It selectively suppresses the growth of HNSCC cells with high oxidative stress resistance while exhibiting only modest effects on less resistant cells and normal keratinocytes. Notably, pimozide exhibited anti-tumor effects as a monotherapy and in combination with paclitaxel at clinically relevant doses. Mechanistic analysis revealed that pimozide rapidly induced ROS accumulation via a mechanism distinct from its known action

SUBMITTER: Okazaki S 

PROVIDER: S-EPMC12861098 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature