Atovaquone-induced activation of the PERK/eIF2α signaling axis mitigates metabolic radiosensitisation.

ABSTRACT:

Background

Hypoxia, a key feature of most solid tumours, including head and neck cancer, reduces radiotherapy efficacy by promoting radiation resistance through micro-environmental and genomic alterations. Addressing these resistance mechanisms is crucial, as radiotherapy remains central to managing locally advanced disease. Atovaquone, a mitochondrial electron transport chain complex III inhibitor, is reported to reduce tumour hypoxia in preclinical models, however, this response does not consistently enhance radiation sensitivity. This work examines the potential of atovaquone to modify the hypoxic response in models of head and neck squamous cell carcinoma (HNSCC), uncovering an adaptive resistance mechanism driven by integrated stress response (ISR) signaling that limits the ra

SUBMITTER: Feng J 

PROVIDER: S-EPMC11967126 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature