August 17, 2018
A class of antitumor compounds known as HDAC inhibitors offer potential for the treatment of ovarian cancer with mutations in the ARID1A gene. Researchers outlined their rationale in a paper published online in Cell Reports.
Already approved by the US Food and Drug Administration (FDA), HDAC inhibitors are used in the treatment of leukemia and other diseases. Ovarian clear cell carcinomas are known for not responding well to conventional chemotherapy, leaving patients with limited treatment options, researchers explained. But in more than half of ovarian clear cell carcinomas, the ARID1A gene is mutated.
According to the study, ovarian cancers with mutations in the ARID1A gene are selectively sensitive to inhibition of the enzyme HDAC2. HDAC2 inhibition halts proliferation and induces programmed cell death in cells with inactivated ARID1A by promoting gene expression of PIK3IP1, a protein that blocks tumor progression.
The study confirmed the therapeutic potential of HDAC inhibitor treatment in mouse models of ARID1A-inactivated ovarian cancer. According to researchers, the HDAC inhibitor slowed tumor growth and abnormal buildup of fluids in the abdomen of tumor-bearing mice and improved survival.
“HDAC2 and associated enzymes are well-established therapeutic targets, and a number of HDAC inhibitors have received FDA approval for the treatment of hematopoietic malignancies,” said lead researcher Rugang Zhang, PhD, deputy director of The Wistar Institute Cancer Center, in a press release. “We suggest that these inhibitors might be repurposed to target ARID1A-mutant ovarian cancers.”
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