Grants - Translational Grants - Maryland - 2014

Andrew Feinberg, M.D., MPH, Philip Cole, M.D., Ph.D.

While genetic mutations, changes in DNA sequence, are central to the development of Cancer, it is increasingly recognized that associated alterations in the chemical structure of the DNA packing material, known as chromatin, are linked to cancer causation. These distinct chromatin states and the molecules that regulate then form the basis of the field of epigenetics.  While epigenetics is generally understood to be important in oncology, it is not yet clear how specific epigenetic changes are generated by different environmental conditions such as UV light exposure. Moreover, it is not understood what epigenetic changes are most impactful for the progression of malignancy and what therapeutic approaches can be used to successfully intervene to prevent or cure cancer. Our team will address how UV exposure in patients can induce particular epigenetic changes in skin lesions, whether existing epigenetic therapies can achieve desired effects of preventing epigenetic changes and progression to cancer, and design and develop new epigenetic therapies that could be useful for skin cancer and other malignancies. We hope to illuminate the factors that dictate patiets’ skin cancer’s responsiveness to epigenetic therapies which could ultimately lead to a new standard of care for treatment. We also plan to synthesize at least one new dual action epigenetic modulator compound that can serve as a clinical candidate for patient cancer trials.