Titles and Affiliations
Division Chief, Breast Medical Oncology
Director, Women’s Cancers Program
Beckman Research Institute of the City of Hope
Research area
Improving the response to immunotherapy and understanding the mechanisms of resistance in aggressive breast cancer.
Impact
Triple-negative breast cancer (TNBC) is an especially aggressive subtype of breast cancer and treatment remains a major clinical challenge. Immunotherapies have been effective against some advanced TNBC, but most patients have not benefitted from current immunotherapy approaches. Dr. Rugo is studying how TNBC and other aggressive breast cancer cells are able to avoid attack by the immune system so that new and better immunotherapies can be developed. Her team discovered that the MYC oncogene is frequently associated with the spread of breast cancer cells to form metastases, development of treatment resistance, reprograming cancer cell metabolism and cell growth, and evasion from the patient’s immune system. They are leveraging liquid biopsy technology to predict metastatic relapse or the development of resistance in patients with aggressive breast cancers and examining a possible connection between these processes and MYC gene activation. They hope to develop ways to improve response to immunotherapy by targeting pathways regulated by the MYC cancer gene.
Progress Thus Far
Circulating tumor DNA (ctDNA) are tiny fragments of a tumor’s DNA that end up in the bloodstream and can be detected by liquid biopsy. Dr. Rugo and her colleagues discovered a strong correlation between ctDNA in the blood, the amount of tumor in the patient’s body, and the response of the tumors to treatment. For their studies, they examined the molecular characteristics of untreated tumor samples from the I-SPY2 trial, focusing on two breast cancer types: hormone receptor (HR)-positive/HER2-negative and triple-negative breast cancer (TNBC). When they compared the gene activity in tumors that released ctDNA with those that did not, they found tumors that shed ctDNA exhibited higher activity in specific gene functions, particularly those regulated by the MYC gene. This suggests MYC may play a role in the release of ctDNA into the blood.
What’s next
In the coming year, Dr. Rugo and her colleagues have two goals: First, discover the connection between ctDNA from patient samples and aggressive breast cancer subtypes, including those that activate the MYC oncogene pathway. Second, to identify treatments that selectively kill MYC-high breast tumor cells to prevent tumor resistance and metastasis. They will build on their progress using single-cell sequencing to compare primary breast tumors and corresponding metastases that have helped to identify upregulation of MYC and alterations in metabolism. Understanding the link between MYC and ctDNA shedding, as well as blocking MYC-related metabolic alterations, can potentially lead to improved therapies for patients with aggressive breast cancer, including better monitoring of treatment response and prediction of recurrence.
Biography
Hope S. Rugo, MD, FASCO is a medical oncologist and hematologist specializing in breast cancer research and treatment. She is Director of the Women’s Cancers
Program and the Division Chief of Breast Medical Oncology at the City of Hope Comprehensive Cancer and across their national network of academic and affiliate sites. At City of Hope, she leverages her expertise in conducting investigator-initiated, consortia, and sponsored trials, working to set priorities for clinical and translational research. Prior to this appointment, Dr. Rugo was at UCSF where she served as the Director of Breast Oncology and Clinical Trials Education at the UCSF Helen Diller Family Comprehensive Cancer Center.
Dr. Rugo is involved in 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.
She previously served as the co-chair of the triple-negative breast cancer working group for the Translational Breast Cancer Research Consortium (TBCRC), facilitating and participating in multi-center translational research trials. She is also a member of the Breast Committee of the Alliance for Clinical Trials in Oncology where she designed and ran a successful cooperative group phase 3 trial involving three pharmaceutical companies. Further, Dr. Rugo has been an investigator with the I-SPY neoadjuvant trials group since its inception thereby actively participated in the design and implementation of I-SPY2. Currently, she is the chair of the Safety Committee for I-SPY2, coordinating safety and toxicity guidelines for each novel agent combination, with real-time monitoring and evaluation of reported toxicities. As a member of the novel agents committee of I-SPY2, Dr. Rugo has mentored young investigators in trial design and conduct.
Dr. Rugo has been recognized for her excellence in both patient care and mentoring the next generation of physicians. She has earned several awards including the ESMO Breast Cancer Award (2024), Master Clinician Award at UCSF (2023), Giants of Cancer Care Award (2020), Women in Oncology Award (2019), and Fellow of the American Society of Clinical Oncology (2017). Dr. Rugo co-chaired an ASCO committee to define previous guidelines for hormonal treatment of metastatic breast cancer and is currently involved in the determination of international oncology guidelines (including NCCN) and several research organizations reflecting a profound commitment to collaborative research. She continues to collaborate with investigators at UCSF with support from a Breast Cancer Research Foundation grant.
