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Barbara A. Parker, MD
Professor Emeritus of Clinical Medicine
Rebecca and John Moores Cancer Center
University of California
San Diego, California
Goal: To identify new therapies for the treatment of drug-resistant and metastatic breast cancer.
Impact: Drs. Parker and Kipps have identified a protein, ROR1, that is associated with aggressive breast cancer and the development of metastases and have generated models that will allow them to study it further. Their findings could inform a new treatment strategy for aggressive breast cancer.
What’s next: The doctors will continue their ongoing studies which includes generating sophisticated patient-derived laboratory models to study the role of ROR1 in breast cancer progression.
While metastatic breast cancer is initially responsive to hormone therapy and chemotherapy, resistance to these therapies develops in most cases. Cells with cancer stem-like properties may contribute to drug resistance and breast cancer recurrence. Drs. Parker and Kipps have identified a protein, ROR1, that is expressed by cancer cells with stem cell-like features making these cells targets for anti-cancer therapy. Dr. Kipps has developed a monoclonal antibody that targets ROR-1. The team is now testing strategies to inhibit ROR1 in animal models and has launched a trial of chemotherapy with the antibody in breast cancer patients. These studies may identify a new treatment strategy for breast cancer.
Full Research Summary
Research area: Developing more effective treatments and treatment strategies for advanced metastatic breast cancer (MBC).
Impact: Metastatic breast cancer is usually not curable, therefore, the goal of treatment is to slow the disease’s growth for as long as possible. This can be achieved with hormone therapy, chemotherapy, and biologic therapy. However, most metastatic breast cancers will eventually develop resistance to these therapies. Drs. Parker and Kipps are investigating mechanisms of resistance and metastasis that will inform better treatments for metastatic breast cancer that could prolong life and improve the quality of life for patients.
Current investigation: The team has been studying ROR1, a protein that is normally expressed in the embryo, but is also found in breast and many other cancers. Breast cancer cells in which ROR1 is present have characteristics of cancer stem cells, which are cells that can regenerate the tumor and may be responsible for metastasis and recurrence, even after apparently successful therapy.
What they’ve learned so far: Their research indicates that ROR1 is expressed by cancer cells with stem cell-like features, and that ROR1 expression correlates with aggressive breast cancer and the development of metastases. Drs. Parker and Kipps have developed a monoclonal antibody called cirmtuzumab that targets ROR1 and interferes with metastasis and cancer growth in laboratory models.
What’s next: Based on their promising finding, the team have launched a clinical trial to evaluate cirmtuzumab in combination with paclitaxel in patients with advanced breast cancer. Their BCRF study will continue to focus on how ROR1 promotes tumor growth and aggressiveness in animal models.
Dr. Barbara Parker is a Professor Emeritus of Clinical Medicine at University of San Diego Moores Cancer Center and former Deputy Director of Cancer Medicine for UC San Diego Moores Cancer Center. She received her medical degree from Stanford University and her postgraduate training in Internal Medicine and Hematology Oncology from UC San Diego. Her practice is devoted to breast cancer and her funded research program involves studies of novel personalized therapies, translational models of breast cancer, molecular features of breast cancer in underserved populations, the impact of lifestyle on breast cancer outcomes, and personalized screening approaches. She serves as the principal investigator for ATHENA Breast Health Network at UCSD where she leads efforts in establishing personalized screening and risk assessment for women at the time of mammography. She is a co-investigator on the ISPY2 clinical trial in high risk early stage breast cancer and serves on the ISPY2 New Agent Selection Committee.