Weei-Chin Lin, MD, PhD

Novel approaches to target MYC in ovarian cancer

Many ovarian cancers express the cancer-causing MYC protein at unusually high levels. The activation of MYC is a hallmark of cancer initiation, progression, and resistance to therapy. Unfortunately, MYC is one of the most difficult proteins to target therapeutically. Development of an effective therapy against MYC activity would lead to new treatment options for ovarian cancer. Although MYC is known to cause platinum resistance in cancer, the detailed mechanisms remain unclear.

Dr. Lin recently discovered that a protein called ACTL6A can both activate MYC and is activated by MYC, meaning that the two proteins form a positive feedback loop. He also found that ACTL6A is responsible for the chemoresistance caused by MYC. Thus, therapies that inhibit MYC and ACTL6A activity might overcome platinum resistance in ovarian cancer. Dr. Lin also uncovered a new way to target MYC activity with small molecule (TopBP1) inhibitors. Based on preliminary data, he hypothesizes that TopBP1 inhibitors might function by enhancing the activity of a protein called MIZ1, which inhibits MYC activity. Thus, enhancement of MIZ1 activity can inhibit MYC activity in ovarian cancer and may be exploited as a therapeutic strategy. In addition to testing this hypothesis, Dr. Lin will explore the possibility that TopBP1 inhibitors might also disrupt the positive feedback loop between MYC and ACTL6A, which contributes to chemoresistance. Identifying a novel approach to target MYC activity will have a major impact on this field of research and could potentially reverse resistance to chemotherapy in ovarian and many other cancers.

Learn more about Dr. Lin’s work on his faculty profile.