Endometrial Cancers Convergence Research Team - Stand Up To Cancer

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SU2C Endometrial Cancers Convergence Research Team:
Responders and Nonresponders to Endometrial Cancers With Mismatch Repair Deficiencies

Grant Term: January 2018–December 2020

This SU2C Endometrial Cancers Convergence Research Team is investigating why only half of all endometrial cancer patients with mismatch repair deficiencies respond to immunotherapy. The team is using patient biopsies from an ongoing clinical trial to figure out how to predict response and side effects and potentially design better immunotherapies for endometrial cancer patients. Mismatch repair deficiencies have been implicated in a wide variety of cancers, including some colorectal, stomach, small intestine, cervix, prostate, bile duct, and liver cancers, neuroendocrine tumors, and uterine sarcomas and ovarian cancers.


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.


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