Evaluation of Intermittent MEK Inhibition in Uveal Melanoma

There is no FDA approved therapy for patients with advanced uveal melanoma, and outcomes are exceedingly poor for this patient population. Our group has demonstrated that inhibition of a cellular pathway called the MAPK pathway with a drug called selumetinib is an effective therapy for uveal melanoma, but, despite this treatment, cures are not achieved. Although drugs such as selumetinib have been studied when patients take the treatment every day, research has shown that, in some cases, it may be better to use the treatment on an intermittent schedule. Such a strategy may reduce the side effects, allow higher doses of the drug to be used, more completely block the MAPK pathway, and prevent the development of drug resistance mechanisms within the tumor. In our proposal, we will conduct a clinical trial that will identify the highest safe dose of selumetinib that can be administered to patients with advanced uveal melanoma on an intermittent schedule, evaluate how well this administration schedule of selumetinib works in patients with uveal melanoma, use tumor biopsy samples to evaluate the downstream effects of this treatment, and explore mechanisms of sensitivity and resistance to further optimize therapeutic approaches to treating patients with this disease and continue our efforts to identify a cure for uveal melanoma.