2003 Early Career Investigator Grant Recipient — Douglas A. Levine, MD

Project Summary

Ovarian Cancer is the leading cause of death from gynecologic malignancies. Over the past decade we have learned much about the causes of hereditary ovarian cancer, but little is known regarding the genetic risk factors for sporadic ovarian cancer. Inherited mutations in two specific genes, BRCA1 and BRCA2, are responsible for approximately 10% of all ovarian cancer. While this is a small fraction of all ovarian cancer cases, women found to have a mutation in one of these two genes have approximately a 40% lifetime risk of developing ovarian cancer. Unfortunately, we are currently unable to predict which women will develop ovarian cancer and who will remain unaffected. One of the goals of this proposal is to help predict which women, of those with inherited mutations, are most likely to develop ovarian cancer. For the remainder of women who develop sporadic ovarian cancer, predisposing genetic factors have not been identified. There is impressive evidence to suggest a relationship between androgens and the development of ovarian cancer in women. This proposal will exploit the aromatase enzyme, a key regulator of androgen levels, to determine if it serves as a risk modifier for ovarian cancer in general and among women with hereditary disease. The scientific approach will capitalize on haplotype blocks, which are recently identified regions of low variation throughout the human genome. Prior to this discovery, studies of genetic variation relied on markers that individually had a relatively low likelihood of significant disease associations. Haplotype-based association studies are a powerful comprehensive approach to identify genetic variation underlying complex diseases like ovarian cancer. This research plan will be one of the first to use this methodology to study genetic predisposition to ovarian cancer. Our findings are expected to aid in the risk stratification and targeting individuals for therapeutic interventions in an effort to reduce the overall burden of ovarian cancer.

Bio

Director, Gynecologic Oncology Head, Gynecology Research Laboratory Professor, Division of Gynecologic Oncology Laura and Isaac Perlmutter Cancer Center New York University Langone Health Douglas A. Levine MD is gynecologic oncologist who specializes in the surgical treatment of women with known or suspected ovarian or uterine cancers. In addition to his clinical practice, Dr. Levine is the current Head of the Gynecology Research Laboratory, where he studies cancer prevention, precision medicine, and rare tumors with unmet needs. He serves as the translational scientist on many national clinical trials determining what genomic alterations are associated with response to targeted therapies. He discovered universal mutations in SMARCA4 that drive small cell carcinoma of the ovary, hypercalcemic type. Dr. Levine has an outstanding level of expertise and leadership in ovarian and endometrial cancer research and a deep commitment to women’s health. Dr. Levine has been very active within the NIH-sponsored Cancer Genome Atlas project (TCGA). He served as co-chair of the ovarian, endometrial, uterine carcinosarcoma, and Pan-GYN disease working groups. He is a member of the Scientific Advisory Committee of the Ovarian Cancer Research Alliance, Clearity Foundation, and Honorable Tina Brozman Foundation. He has authored or co-authored more than 220 peer-reviewed articles and two textbooks. Dr. Levine has received funding from the National Cancer Institute, the Department of Defense, Stand Up 2 Cancer, and the Gynecologic Oncology Group. He has been awarded the American Congress of Obstetricians and Gynecologists Mentor Award, served as co-chair of the American Association for Cancer Research Special Conferences on Ovarian and Endometrial Cancers, received the Foundation for Women's Cancer Excellence in Ovarian Cancer Research Prize, is the Assistant Dean of the Department of Defense Ovarian Cancer Academy, the translational science co-chair of the NRG Oncology Corpus Committee, a member of the NCI Cancer Prevention Steering Committee, and Chair of the NCI Cancer Biomarkers Study Section.