Gordon ChanPronouns: he/him
- Faculty: Medicine & Dentistry-Oncology
- Position: Associate Professor
- Research Areas: basic and laboratory sciences, biochemistry and molecular biology (DNA/ RNA/ proteins/ enzymes), Breast cancer, cancer and neoplastic health, Gynecologic cancers
- Research Theme: Lifelong Women's Health
Summary:
Mitosis is driven by the cell cycle kinase complex Cdk1/cyclin B. Cdk1 activity is required for every aspect of cell division. Cdk1 activity is tightly regulated to ensure that mitosis only occur when cells are ready. Myt1 and Wee1 are kinases that inhibit Cdk1 to prevent premature entry into mitosis. Premature entry into mitosis can lead to mitotic catastrophe, a key mechanism of cancer cells killing by chemotherapy and radiation treatment. Wee1 kinase is overexpressed in a variety of cancers and a small molecule inhibitor, Adavosertib, has been developed as a cancer therapeutic agent. Adavosertib is currently in Phase I/II clinical trial for a variety of cancers (including breast cancers). Some cancer cells are resistant to Adavosertib treatment and the mechanism of resistance is under investigation. We found that Myt1 mediates Adavosertib resistance in breast cancers. Inhibition of Myt1 overcomes Adavosertib resistance in breast cancer cells. We propose to examine Myt1 to understand how it mediates Adavosertib resistance in breast cancer cells. We are also investigating a newly developed Myt1 small molecule inhibitor as a potential combination therapy for breast cancers.