Wistar researchers have found rationale for repurposing a class of antitumor compounds called HDAC inhibitors, already approved by the FDA for the treatment of diseases such as leukemia, as a new therapeutic option for ovarian cancer with mutations in the ARID1A gene. Study results were published online in Cell Reports.
Wistar researchers have found rationale for repurposing a class of antitumor compounds called HDAC inhibitors, already approved by the FDA for the treatment of diseases such as leukemia, as a new therapeutic option for ovarian cancer with mutations in the ARID1A gene. Study results were published online in Cell Reports.
Ovarian cancer is the most lethal gynecological malignancy and the clear cell subtype is particularly notorious for not responding well to conventional chemotherapy, leaving limited treatment options for these patients. The ARID1A gene is mutated in more than 50 percent of cases of ovarian clear cell carcinoma. In normal cells, ARID1A regulates expression of a set of genes by affecting the structure of chromatin – the complex of DNA and proteins in which DNA is packaged in our cells. ARID1A mutations cause loss of the protein or its function, which results in malignant transformation of the cells.
In this study, lead researcher Rugang Zhang, Ph.D., and colleagues showed that ARID1A-mutant ovarian cancers are selectively sensitive to inhibition of another chromatin remodeling enzyme called HDAC2. This finding is consistent with the fact that high HDAC2 expression is known to be associated with poor outcome in this type of cancer.
"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 Zhang, deputy director of The Wistar Institute Cancer Center, and professor and co-program leader of the Gene Expression and Regulation Program. "We suggest that these inhibitors might be repurposed to target ARID1A-mutant ovarian cancers."
Read more at The Wistar Institute
Image: This is Rugang Zhang, Ph.D. (Credit: The Wistar Institute)
