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 focus on identifying new therapeutic targets that will specifically eliminate breast CSCs and biomarkers to signal which patients at risk of 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 recently developed a new algorithm that enables them to identify a population of breast CSCs that are the main driver of metastasis. They are continuing to advance their work on developing small molecules that target CSCs to treat triple-negative breast cancer tumors highly resistant to current therapies. Importantly, these small molecules function by first killing breast CSCs and then activate anti-tumor T-cells, or immune cells already present in the body that can also function against tumors. They may also be less toxic than standard therapies.
In the next year, Dr. Clarke’s team will continue to develop the small molecule inhibitors that may lead to potential clinical compounds. They will also continue their efforts on the molecular regulators of therapy resistance. Understanding how breast cancer overcomes therapeutics, even those that regulate immunity, will provide the team with key insights into developing their new therapeutic strategies.
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, and 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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