PHILADELPHIA (December 16, 2020)—A team of scientists from Fox Chase Cancer Center received a pilot award from the Melanoma Research Alliance (MRA) for a research project that will investigate a new drug target for the treatment of melanoma that combines aspects of epigenetics and immunotherapy.
“We are very excited about receiving this grant, because we really think this could be a new approach for the treatment of melanoma,” said Alfonso Bellacosa, MD, PhD, professor in the Cancer Epigenetics program at Fox Chase. He is the principal investigator for the project, which will include other researchers from Fox Chase, including Tim J. Yen, PhD, James S. Duncan, PhD, John Karanicolas, PhD, and scientists from the Wistar Institute and Yale University.
Epigenetics explores how the expression of DNA can be changed without changing its structure, which is key to preventing diseases and creating treatments for them. Immunotherapy is a class of biological therapies that optimizes the tools of the body’s immune system to fight cancer more effectively.
The project will focus on thymine DNA glycosylase (TDG), a well-known DNA repair enzyme that the Bellacosa lab identified as an important epigenetic factor. In the research proposal, the research team hypothesized that “TDG is a new drug target—at the interface of epigenetic and immune therapy—that is critical for the survival of melanoma cells; TDG inhibition may subvert innate anti-PD1 resistance and sensitize a fraction of metastatic melanoma patients to immunotherapy.”
The proposal goes on to state that TDG inhibitors would be first-in-class epigenetic drugs, which could represent transformative therapeutics for metastatic melanoma.
“We have the strong suspicion,” Bellacosa said, “that if we block TDG, not only will it slow the growth of the melanoma cells, but we can actually render them more inflammatory so they could become recognized by the immune system with the help of immunotherapy.”
The grant includes funding of $50,000 per year through 2022. The grant award comes from MRA’s Request for Proposals, which “calls for ideas that have the potential to lead to near-term clinical application in melanoma prevention, detection, diagnosis, staging, and treatment.”