The Clearity Foundation is proud to announce that our Scientific Advisory Board (SAB) Chair, Dr. Beth Karlan of Cedars-Sinai Medical Center, is the recipient of the 2016 Program Project Development Award. She submitted her work on the ‘Co-Evolution of Epithelial Ovarian Cancer and Tumor Stroma.’ Dr. Beth Karlan’s research focuses on better understanding the co-dependence between ovarian cancer cells and tumor stroma, which can be thought of as scaffolding that is crucial for tumor development and growth. Below is a summary of her project and a short bio.
High Grade Serous Carcinoma (HGSC) is among the most lethal cancers affecting women in the U.S. While most therapeutic approaches in HGSC have focused on malignant epithelial tumor cells and their genetic alterations, it is becoming increasingly clear that the tumor microenvironment plays an equally important role in tumor evolution. We now recognize that the microenvironment serves not only as a scaffold for tissue organization and integrity but also provides key biomechanical and molecular signals that can affect every aspect of tumor growth and biology – including proliferation, survival, metabolism, stem cell fate, and response to chemotherapy. The presence of cancer cells induces a reaction in the surrounding stromal cells similar to fibrosis after an injury. These reactions can also reduce therapeutic efficacy of chemotherapy by creating a barrier for drug transport, while providing a protective environment for cancer cells to repopulate after completion of treatment. Our goal is to demonstrate that anti-cancer therapies should target not only malignant cancer cells but also the microenvironment that fosters tumor growth and survival (stromal cells). Our team of experts, led by Dr. Beth Y. Karlan, will accomplish this through three closely integrated projects that will test the hypothesis that activated stroma helps to drive ovarian cancer growth by triggering and supporting proliferative and metabolic pathways in adjacent cancer cells. Project 1 will test if reprogramming the activated stroma can improve therapeutic efficacy and prevent tumor recurrence. Project 2 will investigate the stroma-induced changes in epithelial ovarian cancer cells that lead to recurrence and chemoresistance. Project 3 will explore the metabolic relationship between tumor cells and activated stroma. All Projects will be supported by a strong Core infrastructure, including preclinical cancer models, pathology, and bioinformatics. We believe that identification of additional molecular sites to target anti-cancer therapeutics could undermine tumor progression and lead to more successful patient outcomes. This project is a collaborative effort that should contribute greatly to the molecular understanding of therapeutically resistant ovarian cancer and translate into more effective interventions in the clinical setting.
Beth Y. Karlan, MD is an internationally renowned physician-scientist and a foremost authority on hereditary gynecologic cancers. She is Director of Cedars-Sinai’s Women’s Cancer Program and Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at UCLA. A graduate of Harvard Medical School, Dr. Karlan’s experience in translational medicine bridges the divide between clinical care and basic research, accelerating “bench to bedside” cancer medicine and bringing patients novel approaches to prevention, early detection and targeted therapeutic interventions. Her work is supported in part by grants from the Department of Defense, the National Cancer Institute, and the American Cancer Society. She is a Presidential appointee to the National Cancer Advisory Board, Editor-in-Chief of two of her specialty’s pre-eminent journals, and an American Cancer Society Clinical Research Professor. Her ongoing efforts include pioneering investigative research on genomic determinants of ovarian cancer, hereditary predisposition to cancer, as well as molecular biomarkers for early detection, treatment and prognostication. She founded the Gilda Radner Hereditary Cancer Program 25 years ago, which has been widely praised for contributing to national ovarian cancer screening guidelines and helping shift the paradigm of testing and counseling for families at risk for BRCA mutations. Dr. Karlan’s advocacy is dedicated to advancing the needs of women with cancer, and in 2005 she helped secure congressional and presidential approval of The Gynecologic Cancer Education and Awareness Act, the first federal support for prevention and awareness programs in women’s cancers.
To read more about Dr. Karlan’s accomplishment, click here.