Michael F. Clarke, MD
Karel and Abice Beekhuis Endowed Professor
2012-2013 BCRF Project:
Professor of Internal Medicine
Associate Director of the Stem and Regenerative Medicine Institute
Palo Alto, California
Using novel technology developed at Stanford University, Dr. Clarke's team has anazlyzed single cancer cells isolated from patients' tumors. They have found a single gene that appears to predict response to chemotherapy in patients with estrogen and progesterone receptor negative, HER2/NEU negative (triple negative) breast cancer. This single test could identify patients with triple negative breast cancer who have a high likelihood of responding to adjuvant therapy, and those who should consider alternative treatments.
Mid-year Progress: 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 to distant sites. These cells are ultimately responsible for cancer-related death in women with this disease. During this funding period, Dr. Clarke's team has made an important finding that may eventually result in decreased mortality from this disease. They have identified the toll-like receptor signaling pathway as a potential therapeutic target for estrogen receptor negative breast cancer. This finding could lead to the identification of new therapies for this poor prognosis group of patients.
After receiving his MD degree from Indiana University, Dr. Clarke was an Oncology Fellow at the National Cancer Institute. In 1986, he joined the faculty at the University of Michigan where he was Professor of Internal Medicine and Professor of Cell and Developmental Biology. In the fall of 2005 Dr. Clarke moved to Stanford University where he directs the solid tumor cancer stem cell program and serves as Associate Director of the Stem and Regenerative Medicine Institute.
While a post-doctoral fellow at the National Cancer Institute, Dr. Clarke was the first to demonstrate that enforced expression of a normal proto-oncogene (c-sis) could lead to transformation (Clarke, et al. Nature, 308: 1984). While at the University of Michigan, Dr. Clarke has made several discoveries relevant to cancer. He was the first to demonstrate that an alternatively spliced proto-oncogene mRNA (mbm2) could function as a dominant-negative inhibitor of the proto-oncogene (Weber, et al. Science, 249: 1990). He was also the first to demonstrate that inhibition of programmed cell death (PCD) was essential for the survival of human breast cancer cells (Clarke, et al. PNAS, 92: 1995).
Most recently, Dr. Clarke's laboratory has made two important findings. He was the first to identify a molecular pathway that regulates the essential process of adult stem cell self-renewal (Park, et al. Nature. 43: 2003). Next, he has found that not all cancer cells found in solid tumors have the capacity to self-renew and form new tumors. His laboratory has developed methods to prospectively identify this "cancer stem cell" population in breast cancer (Al-Hajj, et al. PNAS 7: 2003). These findings have linked the process of self-renewal in normal stem cells to cancer. These observations have implications for the treatment and diagnosis of human cancers. The focus of the laboratories research efforts are directed at the identification and eradication of breast cancer stem cells, the cells that drive the growth and metastasis of these tumors.