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Get ready for an exciting announcement for the melanoma community

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GPER Signaling in Melanoma

Todd Ridky, MD, PhD

Award Type Established Investigator Award
Institution University of Pennsylvania
Description:

Melanoma immunotherapy works by stimulating immune cells to kill tumor. In many cases, immune cells are drawn to tumor by immunogenic proteins on the surface of tumor cells that are also present on normal skin melanocytes, but absent on other cell types. For this reason, many patients who respond to immune therapy also develop vitiligo in skin that is otherwise normal. We hypothesize that drugs that increase the amount of these immunogenic melanocyte proteins will make tumor cells more visible, and therefore more vulnerable, to killing by immune cells. In preliminary experiments we determined that G-1, a small molecule related to estrogen (but that doesn’t have regular estrogen effects) acts on melanoma cells to slow proliferation and increase expression of the immunogenic proteins. When given to mice with melanoma, G-1 cooperated with the immunotherapy drug aPD-1 to dramatically extend survival beyond that seen with either agent alone. The G-1 effects on melanoma cells are mediated through a specific cell surface receptor on the tumor cells called GPER that has not been targeted with FDA approved drugs for any condition. Thus G-1 may be the first example of an entirely new class of medicines that are useful against melanoma. When administered to animals, G-1 was extremely well-tolerated and no adverse side-effects or toxicity was observed. If successful, the studies described in this work will provide much of the data needed to start a melanoma trial to determine whether G-1 cooperates with currently used immunotherapy approaches to further extend survival.