Although most ovarian cancer tumors initially respond to chemotherapy, the cancer typically returns because the tumor becomes resistant to the drugs. Unfortunately, few treatments are available for patients with recurrent disease. Dr. Nephew is studying a new type of drug that might make ovarian cancer cells sensitive to chemotherapy in recurrent disease. The drug removes chemicals, called methyl groups, on the DNA of ovarian cancer tumor cells. By eliminating the methyl groups, the drug is believed to stop the cancer cell growth. Dr. Nephew also will try to determine if this drug plus standard chemotherapy prevents recurrence in patients undergoing their first round of treatment. Dr. Nephew has evidence that recurrence occurs because a population of cancer cells, called ovarian cancer stem cells, are resistant to chemotherapy and these rare stem cells keep the tumor growing. Stem cell growth may also be controlled by methyl groups on their DNA. Eliminating the methyl groups with the drug may kill the stem cells and prevent the tumor from recurring. His research is the first to examine whether these drugs that target methyl groups can destroy the stem cells.
- Daniela Matei, MD
- John Turchi, PhD
Professor of Cellular and Integrative Physiology
Professor of Obstetrics and Gynecology
Indiana University School of Medicine
Assistant Director for Basic Science Research
Indiana University Simon Cancer Center
Dr. Nephew is a Professor of Cellular and Integrative Physiology and Obstetrics and Gynecology at Indiana University. He leads the Ovarian Cancer Research Group at the IU Simon Cancer Center (IUSCC), serves as the Assistant Director for Basic Science Research Bloomington, and is a Program Leader of the Walther Cancer Institute, which is affiliated with IU. He is a Full Member of the Tumor Microenvironment and Metastasis Program and the Breast Cancer Program at IUSCC. Dr. Nephew is the former Director of Graduate Education for the Medical Sciences at IU and is highly active in training and educating graduate and medical students in ovarian cancer research. He is the 2016 Indiana University Graduate School Faculty Mentor Award Winner. Professor Nephew joined Indiana University in 1996. He has dedicated his entire professional career to the study of ovarian cancer. Dr. Nephew’s ovarian cancer research has been continuously funded by National Institutes of Health (NIH)/National Cancer Institute (NCI) since 1996. He is the Principal Investigator and co-investigator on numerous grants from National Institutes of Health/National Cancer Institute (NIH/NCI), serves on various editorial boards, scientific advisory committees, and review panels for both the NIH, American Cancer Society (ACS), and Department of Defense Ovarian Cancer Research Program.
Dr. Nephew’s ovarian cancer research focuses on disease recurrence, and its resistance to chemotherapy. Dr. Nephew has made important contributions defining the characteristics of ovarian cancer stem cells and proposing new strategies to inhibit them. A new paradigm explaining tumor relapse involves the persistence of cancer stem cells. Dr. Nephew is a leader in the field characterizing these malignant cells in ovarian cancer. His collaborative team defined the first phenotype of ovarian cancer stem cells from patient samples. He has shown that ovarian cancer stem cells are chemotherapy resistant and likely responsible for secondary recurrences. His research to target these causative cells in ovarian tumors may enhance the potential to eradicate ovarian cancer. Toward this goal, his laboratory showed that targeting the epigenome, including aberrant DNA methylation (an “epigenetic hallmark” of most cancers including ovarian cancer) inhibited the outgrowth of ovarian cancer stem cells and delayed tumor recurrence. The project is designed to identify and target “epigenetic vulnerabilities” found in the pool of ovarian cancer stem cells that remains after platinum therapy. We will identify how key pathways are epigenetically maintained and regulated in ovarian cancer stem cells. These “epigenetic vulnerabilities” can then be targeted to switch off paths responsible for ovarian cancer stem cell survival after platinum therapy, eradicate the disease and improve the outcome for recurrent ovarian cancer patients.
Dr. Nephew received his undergraduate and graduate (PhD) degrees in Reproductive Physiology from the Ohio State University. He subsequently obtained postdoctoral training in cancer biology at the University of Kansas School of Medicine and then the University of Cincinnati College of Medicine, where he was supported by ACS and NIH postdoctoral fellowships.