New therapeutic strategy discovered for ovarian cancer

Ovarian cancer is the deadliest of all cancers affecting the female reproductive system with very few effective treatments available. Prognosis is even worse among patients with certain subtypes of the disease. Now, researchers at The Wistar Institute have identified a new therapeutic target in a particularly aggressive form of ovarian cancer, paving the way for what could be the first effective targeted therapy of its kind for the disease.

The findings were published online by the journal Nature Medicine.

Ovarian cancer is divided into four different histological subtypes. One of the subtypes is ovarian clear cell carcinoma, which affects approximately 5 to 10 percent of American ovarian cancer patients and about 20 percent of patients in Asia. While most patients with ovarian cancer initially respond well to standard-care platinum-based chemotherapy, the response rate among those with the clear cell subtype is typically low and there is currently no effective therapy for these patients. This underscores the need for a new approach to treating this deadly disease.

"One of the significant challenges with the treatment of ovarian cancer is finding a suitable target that effectively halts the progression of the disease in a personalized manner based on one's genetic makeup," said Rugang Zhang, Ph.D., associate professor in Wistar's Gene Expression and Regulation Program and corresponding author of the study.

"With this study, we have done just that. For patients with this particular subtype, this newly discovered targeted approach may eventually lead to the first effective targeted therapy they've ever had."

The team at Wistar began by looking at ARID1A, a chromatin remodeler. When functioning normally, ARID1A makes it possible for chromatin - a cellular structure that holds DNA together in our cells - to open up and allow our cells to receive commands. This process dictates our cells' behavior and prevents them from becoming cancerous. However, recent studies have shown that ARID1A is mutated in more than 50 percent of cases of ovarian clear cell carcinoma. In fact, ARID1A has one of the highest mutation rates among all types of human cancer. To date, though, no therapies designed to target this common mutation have been described.

Ovarian cancer is any cancerous growth that may occur in different parts of the ovary. The majority of ovarian cancers arise from the epithelium (outer lining) of the ovary. According to the American Cancer Society it is the 8th most common cancer among women in the USA (excluding non-melanoma skin cancers). In the UK ovarian cancer is the fifth most common cancer among females, after breast cancer, bowel cancer, lung cancer and uterine cancer (cancer of the uterus).

Approximately 5,500 women in the UK and 21,000 women in the USA are diagnosed with ovarian cancer each year. Worldwide, around 140,000 women die of ovarian cancer every year.