Researchers at the Wistar Institute say that they have zeroed in on a potential new therapeutic target for a subset of the most aggressive cases of ovarian cancer. And they're heralding the discovery as a big step toward the first effective therapy for the lethal disease.
To get to their conclusion, the investigators started by noting that there are four basic subtypes of ovarian cancer, with ovarian clear cell carcinoma accounting for anywhere from 5% to 20% of all patients suffering from the cancer. The chromatin remodeler ARID1a is mutated in up to half of all cases in this subgroup. And the enzyme EZH2--a target that has already attracted the attention of at least two biotechs--plays what they consider a key role in driving the disease.
By inhibiting EZH2 in experimental models of the disease, the team says they were able to spur regression in ovarian tumors, a specific response that wasn't repeated when they tried this approach with other subtypes.
The findings were published online by the journal Nature Medicine.
"With EZH2 inhibitors currently in clinical development, we believe that our findings will have far-reaching implications," said Benjamin Bitler, a member of the Zhang laboratory, an American Cancer Society postdoctoral fellowship recipient, and first author of the study. "Excitingly, this study provides a much-needed therapeutic strategy for clear cell ovarian cancer and can be utilized to aid in the identification of patients that could benefit from EZH2 inhibition therapy."
Both Constellation Pharmaceuticals, which has been partnered with Genentech, and Epizyme have been working on new drugs that inhibit EZH2, pursuing the notion that
"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, an 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."
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