Posted October 6, 2015
Sandra Orsulic, Ph.D., Cedars-Sinai Medical Center, Los Angeles, California
Surgical cytoreduction (removal of all visible tumor nodules) followed by chemotherapy is the standard treatment for patients with advanced stage epithelial ovarian cancer (EOC). However, a subset of patients cannot be successfully cytoreduced and/or develop resistance to chemotherapy within one year from initial treatment. If clinicians could identify this specific group of patients from the outset, they would be able to provide them with alternative treatments, such as enrollment into clinical trials or treatment with experimental therapeutics. In an effort to uncover novel biomarkers for ovarian cancer, Dr. Sandra Orsulic, FY13 Clinical Translational Leverage Award recipient, and her team are seeking to determine key processes in metastatic ovarian cancer progression that have the ability to identify patients who are unlikely to benefit from standard surgery and/or chemotherapy.
Analyzing gene signatures in primary advanced stage EOC samples from public ovarian cancer datasets, Dr. Orsulic and her team have identified a series of genes whose presence in the tumor microenvironment correlated with metastatic progression, cancer recurrence, and poor patient survival. Their most recent finding was the identification of ADAM metallopeptidase domain 12 (ADAM12) as a gene associated with an aggressive disease course. High protein levels of ADAM12 in banked preoperative sera were associated with decreased progression-free and overall survival outcomes. This approach to detecting possible biomarkers in advanced stage EOC will identify patients with adverse outcomes and has the potential to not only reduce the human costs of ineffective therapies and associated toxicities but also to improve the quality of life for patients living with ovarian cancer by delivering more effective targeted therapies.
Cheon DJ, Li AJ, Beach JA, Walts AE, Tran H, Lester J, Karlan BY, and Orsulic S. 2015. ADAM12 is a prognostic factor associated with an aggressive molecular subtype of high-grade serous ovarian carcinoma. Carcinogenesis 36(7):739-747.