It has been observed that cancers that harbor many mutations are more responsive to treatment with immunotherapies. Tumors that are DNA mismatch repair deficient (MMR-deficient) and microsatellite instability high (MSI-H) have more mutations than other cancers as two mechanisms for repairing DNA damage are malfunctioning. In MMR-deficient, MSI-high endometrial cancers, only about half of all patients respond to immunotherapy treatments, but it is not clear why.
To address this, the SU2C Endometrial Cancers Convergence Research Team is developing novel computational methods to compare biopsies from an ongoing clinical trial. The comparisons seek to identify the differences between patients who respond to treatment and those who do not. In addition, the team is searching for ways to predict who will develop side effects to immunotherapy so that these can be mitigated. Finally, the team is using this information to identify the neoantigens, or protein flags that are present on cancer cells, that are strongly recognized by the immune system.
Taken together, this information will help identify patients who will respond to anti-PD1 treatment, allow expected side effects to be mitigated in advance, and build a foundation for new treatment approaches for those who likely will not respond to the current standard of care.