Genomics of radiation sensitivity in squamous cell carcinomas

Radiotherapy is an important modality in the management of squamous cell cancers with 50% of patients receiving radiotherapy at some point. Despite technological advances, the risk of severe toxicity in a proportion of radiosensitive patients limits radiation doses that can be safely prescribed affecting the potential for cure. While comorbidities, lifestyle and treatment factors can influence interindividual variations, genetic factors are thought to play a major role, accounting for approximately 80% of the variance observed. Over the last decade, substantial progress has been made in the field of radiogenomics, with compelling associations for SNPs identified in genes involved in DNA-damage response, cell-cycle control, apoptosis, antioxidant defenses and cytokine production. Future research efforts should be collaborative, focused on validating and broadening their clinical applicability. Numerous obstacles exist to the clinical application of this knowledge, which need to be overcome before personalized radiation therapy becomes a routine component of oncologic care.