Hope S. Rugo, MD

Dr. Rugo's research has focused on two areas: 1. understanding and reversing resistance to anti-angiogenic therapy (treatment designed to block tumor blood vessel growth) and 2. evaluating genetic changes in circulating tumor cells in patients with advanced breast cancer. In 2012-2013, her studies will focus on two aims. The first is based on earlier experimental and clinical studies indicating that breast cancer is enhanced when tumors are heavily infiltrated by immune cells (specifically macrophages) and angiogenic, or new blood vessels. Since the ability to achieve long-term tumor repression is limited by tumor cells that escape killing by our body's natural defense system, white blood cells or T cells, Dr. Rugo's team will examine a novel therapeutic strategy that blocks factors enabling tumor cells to escape T cell killing, in combination with macrophage-blockade, chemotherapy and anti-angiogenic therapy.

In their second aim, Dr. Rugo's team has demonstrated that it is feasible to isolate and study individual circulating tumor cells. They plan to compare circulating tumor cells and the primary tumor from which they originated. They will continue to further characterize these tumor cells to understand how aggressive cancer cells spread through the blood to other parts of the body.

Mid-year Progress: Novel immunotherapeutic approaches to combat breast cancer now include cell-based, DNA or peptide-based vaccines, as well as therapeutics to cripple cell-based pathways that inhibit tumor cell killing by CD8+ T cells. Dr. Rugo's studies have identified several of these pathways and have led them to examine macrophage-targeted therapies in clinical trials, in combination with chemotherapy, to improve outcome for patients with breast cancer. Macrophages are a type of immune cell important for the body's defense against infection and cancer. The researchers will examine macrophage-antagonists and chemotherapy, in combination with novel therapeutic agents that block "off signals" on CD8+ T cells (programmed cell death (PD) protein) in preclinical models of mammary cancer development. The overall goal of these studies is to identify combinations of immune-based therapies that will provide durable-tumor repression for patients with breast cancer. Dr. Rugo's team has completed the first set of laboratory model studies, evaluating the impact of blocking PD, alone or in combination with a common chemotherapy agent for breast cancer, paclitaxel, and in combination with a macrophage inhibitor. They are now in the process of analyzing encouraging preliminary results suggesting improved tumor suppression with combined therapy. These strategies can be directly applied to the treatment of human cancers if successful.

Also, isolation and molecular analysis of CTCs offer a unique opportunity to monitor cancer progression and/or therapeutic efficacy of targeted therapies in a relatively non-invasive manner. However, since CTCs are extremely rare, isolating these tumor cells away from blood cells poses major technical challenges. Dr. Rugo's team recently published a report describing a novel approach to isolate highly pure CTCs. They also reported on the identification of chromosome abnormalities that were common to these metastatic cells, showing that CTCs are clonally-related to the primary tumors that were removed years prior to recurrence disease. Their ongoing work with RNA expression profiling revealed the "turning on" of cancer-related genes in CTCs; thus providing evidence that these cells are truly malignant in nature. Based on RNA expression data, Dr. Rugo's group found that CTCs clustered into three groups. They continue to investigate the biological and clinical significance of these clusters. Furthermore, preliminary data from their pilot experiments showed that it is feasible to characterize mutations in CTCs. Information from the genetic material (DNA and RNA) of CTCs may be used to explore molecular events associated with breast cancer progression, and may provide more detailed CTC-based biomarkers for clinical trials as well as therapeutic targets. Understanding the molecular nature of CTCs may allow clinicians to specifically target these cells in the context of a personalized treatment.

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.