By Merin C. MacDonald | Date published: December 16, 2024
Targeting Mutant IDH1 to Enhance Anti-Tumor Immunity
Mutations in IDH1 occur in certain brain and liver cancers as well as in leukemia, and these mutations help cancer cells evade the immune system. Mutant IDH1 inhibitors, drugs already approved for clinical use, were previously known to slow tumor growth, but their exact mechanism was unclear.
In a study published in Science, Meng-Ju Wu, PhD, assistant professor of medicine in the Division of Gastroenterology, and colleagues, discovered that these drugs "trick" cancer cells into behaving like they are infected by a virus. This phenomenon, known as "viral mimicry," activates the immune system's antiviral defenses, which then target and destroy the tumor cells. The process is driven by the reactivation of dormant ancient viral elements embedded in the genome, which are normally silenced. When treated with mutant IDH1 inhibitors, these elements become active, producing viral-like signals that trigger immune responses.
This finding opens up new possibilities for enhancing cancer treatments by combining mutant IDH1 inhibitors with immunotherapies. It also sheds light on how these cancers evade immune detection, suggesting new strategies to improve patient outcomes.
“This research highlights the hidden vulnerabilities of cancer cells and how we can leverage them to boost the immune system's fight against tumors,” said Dr. Wu. “By turning the tumor's own defenses against it, we are paving the way for more effective and innovative cancer therapies.”
Dr. Wu’s study was also recently featured in the Clinical Implications of Basic Research section of The New England Journal of Medicine.