April 6, 2012

Factor sensitizes cancer to radiation

Measuring levels of an enzyme in head and neck tumors may indicate how the tumor will respond to radiation therapy.

(Wellcome Images)

Head and neck cancers have repeatedly been linked to infection with human papillomavirus (HPV), with more than half of oropharyngeal squamous cell carcinomas (HNSCCs) positive for HPV. Interestingly, HPV-positive HNSCCs respond better to radiation therapy and have a better prognosis than HPV-negative tumors. But the molecular pathways responsible for their different sensitivities are unclear.

In the March 1 issue of Clinical Cancer Research, Natalia Issaeva, research assistant professor of otolaryngology, and colleagues report that an enzyme called SMG-1 (which participates in sensing DNA damage and is thought to be a tumor suppressor) may play a key role. They found that HPV-positive HNSCC cells and tumors have reduced expression of SMG-1 – and that low SMG-1 expression correlates with positive HPV status and improved patient survival. Depleting SMG-1 in HPV-negative cells increased their sensitivity to radiation, whereas overexpressing the protein in HPV-positive cells protected them from radiation therapy.

The results suggest that assessing SMG-1 levels in tumor biopsies may help to predict how likely a patient’s tumor is to respond to radiation therapy.

The work was supported by an endowment provided to the Barry Baker Laboratory for Head and Neck Oncology at Vanderbilt University.