Karel and Avice Beekhuis Endowed Professor in Cancer Biology
Professor of Internal Medicine
Associate Director, Stem and Regenerative Medicine Institute
Stanford Cancer Institute
Identifying effective methods for targeting cancer stem cells which play a significant role in breast cancer recurrence and metastasis.
Despite advances in the early detection and treatment of breast cancer, many patients will experience a recurrence, sometimes years after the treatment of their primary cancer. Dr. Clarke’s laboratory was the first to identify breast cancer stem cells (CSCs) as major contributors to metastasis—the spread of breast cancer to distant sites. CSCs are also potential drivers of recurrence because of their ability to survive cancer therapy and lie dormant for many years. CSCs are a minor population within tumors but eliminating them may be required to prevent cancer from returning. Dr. Clarke and his team’s work focuses on identifying new therapeutic targets that will specifically eliminate breast CSCs, as well as biomarkers to signal which patients will require adjuvant therapy to prevent breast cancer recurrence.
A major challenge in developing therapies targeting CSCs is that they are very similar to normal stem cells. Hence, new treatments must be specific to the CSCs to avoid serious side effects. Dr. Clarke’s team developed a method to distinguish CSCs from normal cells, and subsequently identified 40 different stem cell targets that could be used to design therapies for triple-negative breast cancer (TNBC) tumors, which are highly resistant to current therapies. They also identified a CSC-specific gene that appears to regulate tumor stem cell survival and is critical for the establishment, maintenance, and growth of tumors. The team is working on a drug to block this gene and they found a few promising candidates, including a drug that effectively hits its target while not affecting normal cells.
In the next year, Dr. Clarke’s team will further refine the drug they developed to eradicate CSCs. This will lay the groundwork for further confirmatory studies in the lab before the drug can progress to a clinical trial.
Michael Clarke, MD is a Professor of Medicine at Stanford University. He is the Karel and Avice Beekhuis Professor in Cancer Biology and Associate Director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. His interest is in Stem Cell Biology. In addition to clinical duties in oncology, Dr. Clarke maintains a laboratory focused on two areas of research: i) the control of self-renewal of normal stem cells and diseases such as cancer and hereditary diseases; and ii) the identification and characterization of cancer stem cells. His laboratory is pursuing how perturbations in the self-renewal machinery contribute to human disease. His focus is to aid in the development of more effective treatment therapies for various forms of cancer.
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