IMAGE: This is Guang Peng, M.D., Ph.D. view more
Credit: MD Anderson Cancer Center
HOUSTON – Functional loss of ARID1a, a frequently mutated tumor suppressor gene, causes deficiencies in normal DNA repair and may sensitize tumors to immune checkpoint blockade therapies, according to researchers from The University of Texas MD Anderson Cancer Center. The preclinical study suggests that mutations in ARID1a could be beneficial in predicting immunotherapy success.
The findings, published today in Nature Medicine, are the first to identify a role for ARID1a in regulating mismatch repair (MMR), a normal process for correcting DNA damage. Further, the study showed that treatment with immune checkpoint inhibitors targeting PD-1 successfully reduced tumor burden and prolonged survival in mouse models with ARID1a-deficient tumors relative to controls.
Mutations in ARID1a occur frequently in a wide spectrum of cancers, with particularly high mutation rates (15-50 percent) in clear cell ovarian cancer, endometrial cancer, gastric cancer and bladder cancer. However, most mutations lead to loss of ARID1a, making it a poor therapeutic target, explained senior author Guang Peng, M.D., Ph.D., associate professor of Clinical Cancer Prevention.
“Since this is a very highly mutated gene in cancer, we wanted to better understand the biological function of ARID1a and potential therapeutic vulnerabilities,”
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