Adam R Karpf, PhD
University of Nebraska Medical Center
2019 Pilot Study Award
Oncogenic collaboration between Cyclin E1 and FOXM1 in high-grade serous ovarian cancer
High-grade serous ovarian cancer is the most common form of ovarian cancer, the most deadly gynecologic malignancy. One of the most important characteristics of HGSOC is genomic instability – when DNA (genome) of cells acquires a lot of mutations and other kinds of abnormalities. Genomic instability is a driving force for the development and evolution of tumors and chemotherapy resistance, and leads to poor patient outcomes. We currently have an incomplete understanding of the underlying causes of genomic instability in ovarian cancer. Dr. Karpf will investigate whether two proteins, cyclin E1 and FOXM1, collaborate to promote genomic instability and cancer formation in ovarian cancer. Both cyclin E1 and FOXM1 have been shown to be present in very high levels in high grade serous ovarian cancer. Dr. Karpf and his colleagues will examine how the level of cyclin E1 and/or FOXM1 in fallopian tube cells effects the genomic instability of cells and the ability of the cells to become cancerous. They will also study the molecular details of how the two proteins interact to bring about these cancer-associated changes. By increasing our understanding of the mechanisms that cause high-grade serous ovarian cancer, this study may lead to new avenues for early detection and treatment of this disease. Importantly, ovarian cancers that result of the mechanism described by Dr. Karpf may be especially vulnerable to treatment with a new class of drugs (e.g. ATR, CHK1, and WEE1 inhibitors) currently being tested for effectiveness in treating ovarian cancer patients.