FTO inhibition enhances the therapeutic index of radiation therapy in head and neck cancer.

ABSTRACT: Despite aggressive chemoradiation treatment, the overall survival rate for patients with HPV- head and neck squamous cell carcinoma (HNSCC) remains poor, highlighting the urgent need for more effective drug-radiotherapy combinations to improve the therapeutic index of radiation therapy (RT). The fat mass and obesity-related gene (FTO) is emerging as a promising cancer therapeutic target; however, its role in the RT response has been underexplored. In our study, we found that both genetic and pharmacologic inhibition of FTO enhanced the efficacy of RT in human and mouse HNSCC tumor xenografts. Mechanistically, inhibition of FTO improved the RT response in HPV- HNSCC cells, which was associated with increased DNA damage, reduced efficiency of homology directed repair, and decreased formation

SUBMITTER: Ji L 

PROVIDER: S-EPMC12220955 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature