Fiona Simpkins, MD
University of Pennsylvania School of Medicine
Circumventing drug resistance mechanisms in CCNE1 amplified ovarian cancers
More than 80% of patients with high-grade serous ovarian cancer (HGSOC) develop resistance to treatment and eventually succumb to their disease. The need to develop new treatments for this form of ovarian cancer is dire. About 65% of ovarian cancers have increased production of a protein called Cyclin E that drives cell division leading to uncontrolled tumor growth. These cancers are among those resistant to current chemotherapy options. Dr. Simpkins and colleagues have discovered a promising new drug combination that kills these cells. Cancer cells with increased Cyclin E accumulate damage to their DNA when it is being replicated (copied), and as a result, they rely heavily on proteins that help pause the replication process and repair the damage to the DNA. Two such proteins are ATR and Wee1. Dr. Simpkins proposes to exploit this weakness in cancer cells with increased Cyclin E to our advantage for ovarian cancer treatment. By blocking ATR and Wee1 from helping the cells repair their DNA, the cancer cells accumulate so much damage that they eventually die. In this study, Dr. Simpkins will find out more about how this drug combination works to kill the cancer cells and test this treatment in mice. Her findings may lead to clinical trials of a new treatment for this aggressive ovarian cancer using already existing chemotherapies.