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

Kim A, Bhardwaj P, Heer CD, Zhao SJ, Lucas KN, Noronha KJ, Friedman S, Morotti R, Sundaram RK, Rehman S, Bhatt D, Dela Cruz FS, Feinberg TY, Ramakrishnan S, Xue W, Barkauskas DA, Hall D, Shern JF, Sun W, Barr FG, Yi JS, Spurrier J, Yu A, Brenner C, Heske CM, Vasquez JC. NAPRT expression and epigenetic regulation in pediatric rhabdomyosarcoma as a potential biomarker for NAMPT inhibition. bioRxiv [Preprint]. 2025 Jul 31:2025.07.28.667284. doi: 10.1101/2025.07.28.667284. PMID: 40766550; PMCID: PMC12324317.

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.