In a study by Yale Cancer Center, researchers report on the discovery of a new role for STimulator of INterferon Genes or STING. STING has traditionally been implicated in the immune response to DNA damage, however, in this study, the focus is on STING’s role in the tumor DNA damage response. The findings may lead to improved treatments, including new combinations of therapies for patients diagnosed with head and neck cancers. The paper is published online today in the journal Nature Communications.
“These results highlight a previously unknown role for STING in regulating the tumor response to DNA-damaging treatments,” said Thomas Hayman, MD, PhD, Assistant Professor of Therapeutic Radiology at Yale Cancer Center and lead author of the study. “Excitingly, our results support the clinical evaluation of STING agonists in combination with DNA-damaging treatments in patients with head and neck cancer to improve responses to standard therapies.”
For this study, utilizing a genetic screening-based approach, researchers including members of the Hayman lab uncovered a new way STING regulates resistance to DNA-damaging cancer therapies. Specifically, scientists show loss of tumor STING blunts the production of treatment-induced reactive oxygen species (ROS) leading to decreased DNA damage, decreased tumor cell death, and ultimately resistance to DNA-damaging therapies. Importantly, an analysis of tumor samples from patients with head and neck squamous cell carcinoma corroborates these preclinical findings and suggests that loss of STING expression correlates with worse clinical outcomes. Finally, Yale researchers add, activation of STING with a clinically available STING agonist increases the effectiveness of radiation therapy to decrease head and neck tumor growth.
Researchers suggest further study of STING as a biomarker for treatment selection is warranted.
“The results are very encouraging, especially bigger picture,” said Joseph Contessa, MD, PhD, Professor of Therapeutic Radiology and of Pharmacology and Co-Leader of the Radiobiology and Radiotherapy Research Program at Yale Cancer Center and senior author of the study. “This work shows us an example of the high risk/ high reward screening experiments that will move our field forward to seek better treatments for a wide range of cancers.”
Funding for the study includes the Head and Neck Cancer Specialized Program of Research Excellence (SPORE) and the K12 Calabresi Immuno-Oncology Training Program (IOTP) at Yale Cancer Center and the Radiological Society of North America (RSNA).