Repurposing Mercaptopurine Through Collateral Lethality to Treat Cancers with Somatic <i>RB1-NUDT15</i> Loss.

ABSTRACT: Somatic retinoblastoma 1 (RB1) loss is prevalent across different cancer types and is enriched in treatment-refractory tumors, such as castration-resistant prostate cancer (CRPC) and small-cell lung cancer, but cannot be considered as a direct druggable target. In this study, we revealed that the close proximity of nudix hydrolase 15 (NUDT15) and RB1 may result in their common somatic codeletion or epigenomic cosilencing in different cancer types and subsequent significant positive correlations of their expressions at the bulk transcriptional and single-cell levels. With clinical CRPC samples, co-loss of RB1 and NUDT15 were commonly observed (14 out of 21). Due to the contribution of NUDT15 deficiency to thiopurine-induced toxicity, exploiting a vu

SUBMITTER: Zhou T 

PROVIDER: S-EPMC12402595 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature