The Yale Cancer Center has discovered a new role for Stimulator of Interferon Genes (STING) in head and neck cancer treatment.
While STING traditionally has been implicated in the immune response to DNA damage, the researchers examined its role in the tumor DNA damage response. The findings may lead to improved treatments, including new combinations of therapies, the researchers said.
“These results highlight a previously unknown role for STING in regulating the tumor response to DNA-damaging treatments,” said lead author Thomas Hayman, MD, PhD, assistant professor of therapeutic radiology at Yale Center.
“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,” said Hayman.
Using a genetic screening-based approach, the researchers uncovered a new way that STING regulates resistance to DNA-damaging cancer therapies. Specifically, they showed how a loss of tumor STING blunts the production of treatment-induced reactive oxygen species leading to decreased DNA damage, decreased tumor cell death, and ultimately resistance to DNA-damaging therapies.
Interestingly, the researchers said, 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, the researchers said, activation of STING with a clinically available STING agonist increases the effectiveness of radiation therapy to decrease head and neck tumor growth. Further study of STING as a biomarker for treatment selection is warranted, the researchers said.
“The results are very encouraging, especially bigger picture,” said Joseph Contessa, MD, PhD, professor of therapeutic radiology and of pharmacology, co-leader of the Radiobiology and Radiotherapy Research Program at the Yale Cancer Center, and senior author.
“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,” said Contessa.
The study, “STING Enhances Cell Death Through Regulation of Reactive Oxygen Species and DNA Damage,” was published by Nature Communications.
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