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Michael F. Clarke, MD
Karel and Abice Beekhuis Endowed Professor
Professor of Internal Medicine
Associate Director, Stem and Regenerative Medicine Institute
Goal: To understand the role of cancer stem cells on tumor cell dormancy, cancer recurrence and metastasis.
Impact: Dr. Clarke’s laboratory was the first to identify breast cancer stem cells as responsible for the growth and spread of breast cancer to distant sites (metastasis). His team is identifying novel therapeutic targets specific for breast cancer stem cells as well as biomarkers that can indicate which patients require adjuvant therapy to prevent breast cancer recurrence. These studies will lead to the development of drugs to target cancer stem cells that are intrinsically resistant to standard therapies and to identify women who are at risk for recurrence and metastasis.
What’s next: Dr. Clarke will follow up on his two novel discoveries: identification of druggable cancer stem cell targets that will be used to develop novel treatments; and characterization of a stem cell specific gene and development of inhibitors of this gene.
Despite advances in the early detection and treatment of breast cancer, many patients will experience a recurrence over their lifetimes, sometimes years after the treatment of their primary cancer. Breast cancer stem cells are thought to be the drivers of recurrence because of their ability to survive cancer therapy and lie dormant for many years. Dr. Clarke is investigating ways to target these cells and is now making small molecule drugs that may eliminate breast cancer stem cells while sparing normal stem cells.
Full Research Summary
Research area: Effectively targeting breast cancer stem cells, which are thought to be the drivers of recurrence, to develop more effective and less toxic therapeutic options for patients.
Impact: Cancer stem cells are resistant to cancer therapies and can remain dormant for many years after treatment. Dr. Clarke's laboratory was the first to identify breast cancer stem cells, a minority population of cancer cells that are responsible for the growth and spread of breast cancer. Dr. Clarke is now analyzing tumor and clinical data with the aim of discovering ways to target these cells that would reduce the risk of recurrence and the number of breast cancer deaths. Dr. Clarke’s research will lead to more effective and less toxic therapeutic options which will greatly impact the outcomes for patients and ultimately eliminate metastatic breast cancer mortality.
Current research: Dr. Clarke and his team will build on his discoveries which identified the first factors on cancer stem cells that could be preferentially targeted while sparing healthy stem cells. They are also expanding their investigations to develop an inhibitor that will prevent drug-resistant breast tumor cells from surviving and metastasizing.
What he’s learned so far: A major challenge in developing novel treatment to target cancer stem cells is that these cells bear substantial similarities to normal stem cells. Hence, novel treatments must be very specific to the cancer stem cells to avoid serious side effects. Dr. Clarke and his colleagues have developed a method to distinguish cancer stem cells from normal cells. This method has enabled the identification of 20 different stem cell targets that can be used to develop novel drugs for the treatment of triple-negative breast cancer (TNBC) tumors which are highly resistant to current therapies. They have also identified a cancer stem cell gene that appears to regulate tumor stem cell survival and is critical for the establishment, maintenance, and growth of tumors. They have shown that this gene plays a role in the regulation of TNBC stem cells but not normal stem cells. Thus, it provides a potential therapeutic target for TNBC tumors. They have developed an inhibitor of this gene and are continuing efforts to develop other small molecule drugs that specifically target the cancer stem cells while sparing normal stem cells.
What’s next: Dr. Clarke has made two novel discoveries that have the potential to be translated into the clinic: identification of druggable cancer stem cell targets for drug development; and characterization of a stem cell specific gene and development of inhibitors of this gene. Notably, these discoveries constitute the first factors to be identified that enable preferential targeting of cancer stem cells but spare other healthy stem cells. His team will continue to pursue these avenues and ultimately translate their findings to the clinic. They are also continuing their studies of a novel pathway shown to be critical in drug-resistance and metastasis. In the coming year, Dr. Clarke will expand his investigations into mechanisms of this pathway to develop an inhibitor that will prevent drug-resistant breast tumor cells from surviving and metastasizing.
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.