2019 Recipient Ronald Buckanovich, MD, PhD

Ronald Buckanovich, MD, PhD

Targeting Tumor Desmoplasia to Enhance Immunotherapy

Project Summary

Approximately 22,400 women in the United States will be diagnosed with ovarian cancer (OvCa) in 2018, and 14,400 will die from the disease, giving OvCa the third-highest mortality:incidence ratio among all cancers. Clearly, novel therapeutic approaches are needed to improve the outcome of OvCa patients. Immunotherapy is one approach to improve the outcomes of women with OvCa. Unfortunately, despite strong evidence of an anti-tumor immune response in many OvCa patients, immune therapies have been underwhelming in this disease, being effective for only 10~15% of women with ovarian cancer. Understanding why these treatment approaches have been ineffective in ovarian cancer is critical to improving the long-term survival of women with ovarian cancer. One reason for the disappointing results with immune therapies may be OvCa’s unique environment.

We recently demonstrated a population of cells known as a carcinoma associated mesenchymal stem cell (CA-MSC), get co-opted by the cancer and creates a dense scar tissue which can prevent cancer fighting immune cells from entering the tumor. Furthermore, CA-MSC can recruiting other cells, known as TAMs, which can inactivate any cancer fighting immune cells which penetrate the dense scar tissue. We thus hypothesize that CA-MSC are a critical therapeutic target to enhance the efficacy of anti-tumor immune therapies.

These studies will evaluate a critical new target to enhance immune therapy. As we are using clinically relevant therapeutics, if successful our studies could be directly translated into the clinic to increase the activity of these game-changing therapies and improve the long-term survival of women with OvCa.

Areas of Research: ,

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.