2004 Recipient Ronald Buckanovich, MD, PhD

Ronald Buckanovich, MD, PhD

Identification and Validation of Clinically Relevant Targets in Ovarian Tumore Vasculature

Project Summary

Tumor blood vessels are different than normal blood vessels. Tumor vessels not only function differently, they also make unique proteins not made by normal blood vessels. With the support of the OCRF we have identified over 70 ovarian tumor vascular specific markers (TVMs). Based upon their tumor specific expression and exposure to blood we believe that these are ideal targets for tumor therapy. One goal of our work is to identify and create antibodies targeting these TVMs which can be used as anti-human ovarian cancer vascular therapeutics. Similarly, based upon their tumor specific expression, expression at the earliest stages of tumor development, and direct exposure to blood, we believe that TVMs are potential biomarkers for not only targeted therapy, but also ovarian cancer diagnosis. The second goal of our study is to determine if TVMs or immune responses against TVMs can be detected in the sera of ovarian cancer patients as disease biomarkers. Finally, tumor vasculature provides critical signals and factors to support the growth of ovarian cancer stem cells; the cells believed to be responsible for the initiation and recurrence of ovarian cancer. This ‘tumor vascular niche’ has been proposed as a potential therapeutic target. The final aim of our current study is to begin to understand the role of ovarian TVMs in supporting cancer stem cell growth and determine if disrupting the tumor vascular niche can disrupt the growth of ovarian cancer stem cells.

Bio

Professor of Medicine Director of the Ovarian Cancer Center of Excellence Co-Director of the Womens Cancer Research Center Magee-Womens Research Institute UPMC Hillman Cancer Center University of Pittsburgh

Ronald Buckanovich graduated from Cornell University in 1990 with a B.S. in Genetics and Biochemistry. He then completed the Medical Scientist Training Program and started his life-long study of ovarian cancer.  He received his Ph.D. in 1996 from the Rockefeller University and his M.D. in 1998 from Cornell University. Dr. Buckanovich then went on to complete an Internal Medicine residency and a Hematology-Oncology fellowship at the Hospital of the University of Pennsylvania. During his fellowship he continued his research on ovarian cancer, identifying dozens of novel clinical targets and helped to develop a novel therapeutic to enhance tumor vaccine therapy. Dr. Buckanovich joined the University of Michigan as ascended to the ranks of Associate Professor.  There he also served an associate director for the Hematology Oncology Fellowship.  In 2017 Dr. Buckanovich was recruited to the Magee Women’s Research Institute and UPMC Hillman Cancer Center of the University of Pittsburgh as a Professor of Medicine and serves as the Director of Ovarian Cancer Center of Excellence and Co-Director of the Women’s Cancer Research Center.  His lab has identified a novel population of cancer stem-like cells (CSCs) which may be responsible for ovarian cancer metastasis, chemotherapy resistance and ultimately disease recurrence.  His laboratory also identified and characterized a novel population of cancer associated mesenchymal stem cells (MSCs)—normal cells recruited by the cancer to help the cancer grow. His laboratory is now studying the factors which regulate CSCs and MSCs including regulators of asymmetric division and quiescence.  His laboratory work has resulted in the initiation of 4 translational clinical trials for the treatment of ovarian cancer.  In addition, his group has identified two novel compounds which are now being developed for first in human clinical trials; one which blocks the ability of cancer cells to metastasize, and a second which selectively kills the cancer stem-like cells to reverse chemotherapy resistance. Based on the knowledge he has gained studying the tumor microenvironment, his group is now also looking at ways to enhance anti-tumor immune therapy by targeting host cells in the tumor.   In addition to his laboratory studies, Dr. Buckanovich has a busy clinical practice, specializing in the treatment of ovarian and uterine cancers. He is currently the principal investigator of two clinical trials at the University of Pittsburgh. He has been an author or co-author of 70 original research articles.  In recognition of his work, Dr. Buckanovich received a Clinical Investigator Award from the Damon Runyon Cancer Research Foundation, the National Institutes of Health New Innovator – Directors Award, Society of Gynecologic Oncology Best Basic Science Award, and he has been elected to the American Society of Clinical Investigators.