University of California
San Francisco, California
Director, Breast Oncology and Clinical Trials Education
UCSF Helen Diller Family Comprehensive Cancer Center
Professor of Medicine
Improving the response to immunotherapy and understanding the mechanisms of resistance in aggressive breast cancer.
Triple-negative breast cancer (TNBC) is an especially aggressive subtype of breast cancer and treatment remains a major clinical challenge. Immunotherapies called checkpoint inhibitors have been effective against some advanced TNBC, but most patients have not received benefit from current immunotherapy approaches. Dr. Rugo is studying how TNBC cells are able to avoid attack by the immune system so that new and better immunotherapies can be developed. Specifically, her team is investigating ways to improve response to immunotherapy by targeting pathways regulated by the MYC cancer gene, which may play a role in preventing immune cells from killing tumor cells. In related work, Dr. Rugo is determining whether serial analysis of circulating tumor DNA (ctDNA) in blood samples can be used to predict metastatic relapse or the development of resistance in patients with aggressive breast cancers. The results of these studies will inform treatment decisions to prevent cancer recurrence and improve treatment outcomes for breast cancer patients.
Dr. Rugo and her team have discovered new vulnerabilities in the treatment of TNBCs, which form the foundation of the current study. They have shown that the MYC cancer gene is an important factor in mediating TNBC disease and other aggressive breast cancers. Building on these findings, her team has discovered that MYC drives breast cancer immune evasion, but this effect can be overcome using a combination of immunotherapies. In her ctDNA studies, Dr. Rugo and her team have shown that patients with a large amount of ctDNA have a greater risk of relapse or metastatic recurrence compared to those with little or no ctDNA.
Dr. Rugo and her colleagues will continue to determine ways to improve immunotherapy for patients with TNBC. This includes ongoing studies to understand how the MYC oncogene may hide tumor cells from a patient’s immune system. In addition, her team will determine the mechanism of action of a specific protein (CDK1) that regulates the cell cycle and MYC gene activation. Her team will also continue to examine how ctDNA dynamics can be used to predict patient outcomes and why some breast tumors shed high amounts of ctDNA while others have undetectable levels. To this end, they will leverage available clinical and gene expression data from a large clinical trial (I-SPY2) to evaluate ctDNA dynamics during neoadjuvant chemotherapy in individual patients and assess its value for predicting metastatic recurrence. They will also attempt to discover genes and pathways that could explain how ctDNA is shed into the blood. Understanding the prognostic impact of ctDNA dynamics and the processes involved in ctDNA shedding may help maximize the use of ctDNA as a biomarker of response and survival.
Hope S. Rugo, MD, FASCO, is a medical oncologist and hematologist specializing in breast cancer research and treatment. A Professor of Medicine, Dr. Rugo joined the Breast Care Center in 1999 after a decade of experience at University of California San Francisco (UCSF) in malignant hematology and bone marrow transplantation for a variety of diseases, including breast cancer. She entered the field of breast cancer in order to incorporate novel therapies based on an understanding of the biology of cancer with excellent quality of care into the treatment of women with breast cancer.
Dr. Rugo is the Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center. She is a principal investigator of multiple clinical trials focusing on combining novel targeted therapeutics with standard treatment to improve the treatment of both early and late stage breast cancer, and has published widely in this area. Her current research interests include immunotherapy and combinations of targeted agents in the treatment of breast cancer to overcome resistance. In addition, Dr. Rugo has conducted a number of studies focusing on reducing toxicity from therapy, resulting in approval of scalp cooling to reduce chemotherapy induced hair loss, and a steroid mouthwash to reduce targeted agent stomatitis. She is an investigator and the chair of the Safety Committee for the multicenter adaptively randomized phase II I-SPY2 trial, and also serves on the Novel Agents Committee. Dr. Rugo is the co-chair of the Triple Negative Working Group and an active member of the Translational Breast Cancer Research Consortium (TBCRC), and is the principal investigator of several TBCRC trials including a multi-center immunotherapy trial funded by the Breast Cancer Research Foundation (BCRF). She is an active member of the Alliance (formerly CALGB) Breast Committee, as well as ASCO, where she serves on the Guidelines Committee and as an editor for the Education Committee.
In addition to her research, Dr. Rugo is an active clinician, and is committed to education, regularly lecturing locally, nationally, and internationally on subjects relating to the treatment of and supportive care for breast cancer. At UCSF, Dr. Rugo runs the Breast Forum, an open bimonthly evening educational session for breast cancer patients, families, and friends from throughout the bay area.
Dr. Rugo graduated from the University of Pennsylvania School of Medicine in 1983. She completed a residency in internal medicine and primary care followed by a fellowship in hematology and oncology at the University of California San Francisco. She was a post-doctoral fellow in immunology participating in laboratory research at Stanford University from 1988-1990. In 1990, Dr. Rugo joined the faculty at UCSF in the Division of Hematology and Oncology. Dr. Rugo has been recognized for her excellence in both patient care and in teaching of both medical students and training physicians. She has received several awards including the Bank of America Giannini Foundation Award and a UCSF Clinical Cancer Center Investigator Research Program intra-mural award. In 2006, she was honored for her work in Breast Cancer Research by the Friends of the Breast Care Center.
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