Ovarian cancer is commonly treated with DNA damaging chemotherapy drugs such as cisplatin. Dineo Khabele, M.D., assistant professor of Obstetrics and Gynecology, and colleagues are exploring the idea of combining cisplatin with histone deacetylase inhibitors (HDACi) – drugs that target enzymes associated with DNA damage and repair.
The researchers previously showed that the HDACi romidepsin (FK228) kills cultured ovarian cancer cells. They have now evaluated FK228 in combination with cisplatin in ovarian cancer in vitro and in vivo (in mice with engrafted ovarian tumors). They found that FK228 enhanced the cell-killing effects of cisplatin in cultured ovarian cancer cells. Mice treated with FK228, cisplatin and both drugs had reduced tumor weights and volumes. In mice, the drug combination induced the greatest level of DNA damage, as assessed by pH2AX – a marker that may be useful for assessing treatment response.
The studies, reported in the December issue of Gynecologic Oncology, provide a foundation for future clinical evaluation of FK228 combined with a platinum-based chemotherapy for treating ovarian cancer.
This research was supported by grants from the National Cancer Institute (CA148887, CA068485, CA091408) and the National Center for Advancing Translational Sciences (TR000445) of the National Institutes of Health and by Celgene Corporation.
