Alfonso Bellacosa, M.D., M.H.S.

Immunotherapy harnesses a patient’s immune system to kill tumor cells. Currently, only one-third of lung cancer patients respond, but we may have found a new way to help non-responders. The cytosine (C) building block of DNA is chemically modified to become methylcytosine (mC), and this turns genes off. We found mC can be low in some cancers, and this turns on cancer-causing genes and genes that make the lung cancer resistant to immunotherapy. We are developing new drugs that inhibit Thymine DNA glycosylase (TDG), an enzyme that converts mC to C. If we block TDG, mC is restored and cancer cells respond to immunotherapy. We will make a mouse model of lung cancer with low mC. We will then use a combination of TDG inhibitor plus immunotherapy to treat mice with lung cancer. This research has the potential of making a long-lasting impact on the treatment of lung cancer.