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Thomas J. Kipps, MD, PhD
Professor of Clinical Medicine
Director, Center for Novel Therapeutics
Evelyn & Edwin Tasch Chair in Cancer Research
University of California
San Diego, California
Goal: To identify new therapies for the treatment of drug-resistant and metastatic breast cancer.
Impact: Drs. Kipps and Parker have identified a protein, ROR1, that is expressed by many cancer types and is associated with aggressive breast cancer and the development of metastases. The team has successfully developed a drug to target ROR1 that they have shown to slow metastatic spread. Understanding the role of ROR1 in drug resistance and breast cancer recurrence could inform new treatment strategies for aggressive disease.
What’s next: The team will continue to use breast cancer models in the lab to identify markers of treatment response or resistance to targeted therapies. Their work has the potential to open new avenues to treat metastatic breast cancer.
While metastatic breast cancer is often initially responsive to hormone therapy and chemotherapy, resistance to these therapies develops in most cases. Cancer stem cells are thought to be responsible for drug resistance and breast cancer recurrence. Drs. Kipps and Parker have identified a protein, ROR1, that is expressed by cancer cells with stem cell-like features that make them targets for anti-cancer therapy. The team is working to find markers of drug response or resistance and develop more effective treatments for advanced metastatic breast cancer.
Full Research Summary
Research area: Developing more effective treatments and treatment strategies for metastatic breast cancer (MBC).
Impact: Because there is no cure for MBC, the goal of treatment is to slow the disease’s growth for as long as possible. This can be achieved with hormone therapy and chemotherapy, but most MBCs will eventually develop resistance to these therapies. Drs. Kipps and Parker are investigating a key protein, ROR1, whose expression correlates with aggressive breast cancer and the development of metastases. The team has developed a monoclonal antibody that targets ROR1. They are now working to identify biomarkers of therapy response and resistance, which could inform the development of better treatments for MBC that would 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. Kipps and Parker have developed a monoclonal antibody called cirmtuzumab that targets ROR1 and is now being tested in clinical trials.
What’s next: The team will continue laboratory studies to develop markers for response or resistance to targeted therapies like cirmtuzumab. Ultimately, they aim to develop more effective treatments and treatment strategies for advanced metastatic breast cancer.
Thomas Kipps, MD, PhD, is Professor of Medicine, Evelyn and Edwin Tasch Chair in Cancer Research, and Deputy Director of Research Operations at the UC San Diego Moores Cancer Center. He received his MD and PhD. in Immunology from Harvard University and had his residency and fellowship training in Internal Medicine, Hematology, and Genetics at Stanford University. Dr. Kipps is internationally renown for his translational research on immunologic approaches for the treatment of cancer and understanding the biologic mechanisms that contribute to cancer, in particular chronic lymphocytic leukemia (CLL). Dr. Kipps has over 25 years’ experience in combining research and clinical care responsibilities. As deputy director of research operations, he is working to integrate basic and translational research at the Moores Cancer Center with basic and translational scientists, clinical investigators, epidemiologists, and physicians, who offer state-of-the art therapies for patients with various forms of cancer. Dr. Kipps directs the multi-institutional, NIH-sponsored CLL Research Consortium (CRC) and directs a Specialized Center of Research in Leukemia supported by the Leukemia & Lymphoma Society. In addition, he is a two-time awardee of the NIH MERIT Award. He also is the principal investigator for a Disease Team III project sponsored by California Institute for Regenerative Medicine, in which he developed a humanized anti-ROR1 monoclonal antibody (mAb), designated UC-961 (or cirmtuzumab), for which he now holds the IND with which to conduct clinical trials examining the safety and efficacy of this mAb in the treatment of patients with cancer.