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Thomas J. Kipps, MD, PhD
Professor of Clinical Medicine
Deputy Director of Research
Evelyn & Edwin Tasch Chair in Cancer Research
University of California
San Diego, California
- Seeking new therapies for the treatment of drug resistant and metastatic breast cancer.
- Laboratory studies are ongoing to advance a promising drug to clinical trials that could improve response to chemotherapies in patients with advanced disease.
- These preclinical studies are poised to move to clinical trials and could impact patients soon.
Early stage breast cancer is treatable with standard therapies, but even after ostensibly curative therapy, the breast cancer can come back many years later. Recurrent breast cancers are often resistant to the drugs used to treat the original tumor. Cancer stem cells are thought to be responsible for drug resistance and breast cancer recurrence. Drs. Kipps and Parker have identified a marker on cancer stem cells that makes them targets for anti-cancer therapy. They are conducting laboratory studies to test strategies to target this marker and kill cancer stem cells.
Full Research Summary
Although initially responsive to hormone therapy and chemotherapy, most metastatic breast cancers will develop resistance to these therapies. Some breast cancers express ROR1, which is a surface protein ordinarily found on cells in embryos, but not on normal adult breast cells. Patients with breast cancers that express ROR1 typically have more aggressive disease.
Drs. Kipps and Parker discovered that 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. The team found that the residual cancer cells remaining after paclitaxel therapy had enriched proportions of cells expressing ROR1 and other cancer stem cell-associated markers.
They have found that a targeted anti-ROR1 drug called cirmtuzumab significantly increased the anti-tumor effect of paclitaxel chemotherapy in breast cancer cells with high ROR1 levels. Cirmtuzumab is a humanized monoclonal antibody targeting ROR1 and is currently in Phase I studies.
This year, the team will continue these efforts in studies from patient samples to determine the relative expression of ROR1 in patient samples and the effect of chemotherapy on increasing cancer stem cells with high levels of ROR1. They will also test a cirmtuzumab drug formulation in breast cancer laboratory models with low or high proportions of ROR1+ tumor cells.
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.