Hope S. Rugo, MD

Antiangiogenic therapy combined with chemotherapy is now a well accepted therapy for metastatic breast cancer, and is being evaluated as a treatment for early stage disease. We are severely limited by the inability to understand tumor sensitivity or resistance to this targeted biologic treatment. In collaboration with Dr. Gabrielle Bergers, Dr. Rugo is studying markers of response and resistance to anti-angiogenic therapy in blood and tumor tissue in a laboratory model of breast cancer, and will apply these findings to clinical samples in the future.

Mammary stem cells have been identified in breast tumors, and these cells have the ability to populate tumors. It may be that slowly dividing stem cells can escape standard therapies for breast cancer and represent the source of recurrent disease. In this project, Dr. Rugo and colleagues are attempting to identify stem cell markers on circulating tumor cells in patients with advanced breast cancer. In peripheral blood these cells are quite rare and the researchers are continuing to improve their methods of identification. Interestingly, they have found a stem cell like cell population in the spinal fluid in patients with known cancer in the brain. They hope to be able to look at genes in these cells based on technology developed at UCSF. Work on this project is ongoing.

Mid-Year Progress Report:
New blood vessel growth stimulated by tumors is critical to the ability of cancers to grow and metastasize. Anti-angiogenic therapy designed to starve tumors of their blood supply is an exciting novel approach to cancer treatment. Although the combination of chemotherapy and the anti-angiogenic agent bevacizumab (Avastin) is approved for the treatment of advanced breast cancer, the benefit from the addition of the targeted agent is modest, without a demonstrated benefit in survival. We know that resistance to anti-angiogenic therapy plays a role in this less than impressive clinical result, but our understanding of the factors that determine both response and resistance to anti-angiogenic agents is extremely limited.

Dr. Rugo and her colleagues are studying markers of response and resistance to various anti-angiogenic therapies in blood and tumor tissue in a laboratory model of breast cancer, and will apply their findings to clinical samples in the future. It appears that blood cells derived from the bone marrow play a role in resistance to at least some forms of anti-angiogenic therapy, and it is possible that reducing these cells with an antibody could restore the sensitivity of the cancer to targeted agent. The researchers’ ongoing work is directed towards a better understanding of these cells, and demonstrating that blocking the cells can reverse resistance. In addition, they are looking at other cells and factors that contribute to resistance. The second part of their project is focused on identifying circulating cancer cells in the blood that might be resistant to standard treatment. If the researchers can characterize these cells, it may be possible to identify effective therapies directed toward the biology of the resistant cells.

Bio:
Hope Rugo is a Clinical Professor of Medicine in the Division of Hematology and Oncology at the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, where she directs the Breast Cancer Clinical Trials Program and has an active clinical practice. Her research interests include novel therapies for advanced breast cancer, evaluation of circulating endothelial and epithelial cells as novel markers of response and resistance to therapy, complementary medicine and supportive care.

Dr. Rugo is an investigator in the Bay Area Spore at UCSF breast cancer center, and the principal investigator of a number of clinical trials. She has published many peer-reviewed papers and has given presentations on a variety of cancer related topics. Dr. Rugo is a member of the CALGB breast core committee and is the principal investigator of a new phase III CALGB therapeutic study for advanced breast cancer.

After graduating summa cum laude from Tufts University, Dr. Rugo received her MD from the University of Pennsylvania and completed both a residency in internal medicine and fellowship in hematology and oncology at UCSF. She also completed a two-year postdoctoral fellowship in immunology at Stanford University.