NAPRT expression and epigenetic regulation in pediatric rhabdomyosarcoma as a potential biomarker for NAMPT inhibition.

ABSTRACT:

Purpose

New treatments are needed to improve survival in children with rhabdomyosarcoma (RMS). NAD⁺ biosynthesis, regulated by the enzymes NAPRT and NAMPT, represents a metabolic vulnerability due to high NAD⁺ turnover in cancers. Although NAMPT inhibitors (NAMPTi) show preclinical promise, clinical translation has been limited by toxicity and the lack of predictive biomarkers. Here, we evaluated NAPRT expression in RMS and its potential as an actionable biomarker to guide NAMPTi therapy.

Experimental design

NAPRT promoter methylation, transcript levels, and protein expression were assessed in RMS cells, PDXs, and primary tumors (n=109) from the Children's Oncology Group. In vitro sensitivity to NAMPTi was tested in molecularly diverse and isogenic RMS cell lines, exa

SUBMITTER: Kim A 

PROVIDER: S-EPMC12324317 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature