Combining MEK inhibition with oncolytic viral therapy as a novel treatment for low grade serous ovarian carcinoma
Low grade serous ovarian cancer (LGSC) is a rare form of ovarian cancer accounting for about 5% of ovarian cancer cases. While LGSC grows relatively slowly, it is stubbornly resistant to almost all therapeutics. As a result, outcomes are very poor, with only 10-20% of patients living more than 10 years. There is an urgent need for creative new treatment strategies for these patients. MEK inhibitors are a type of targeted therapy tested in LGSC, targeting a cellular pathway known to be defective in these cancers. However, response rates are poor.
Dr. Huntsman recently found that LGSC tumors are defective in a pathway that protects cells against viruses. Because of this, LGSC may be particularly susceptible to oncolytic viral therapy. Oncolytic viruses are engineered to kill tumor cells, with no effect on healthy cells. Importantly, a recent study has shown that in melanoma, treatment with MEK inhibitors increases the effectiveness of oncolytic viruses. For this Pilot Study project, Dr. Huntsman will therefore test whether treating LGSC simultaneously with MEK inhibitors and oncolytic viruses has a greater impact than either agent alone. Since both MEK inhibitors and oncolytic viruses have been used clinically, this study has high potential to progress rapidly to clinical trials and improve outcomes for this rare and difficult-to-treat form of ovarian cancer.