News Reports; March 2007

By Querida Anderson and John D. Zoidis, MD
Published: Monday, Aug 16, 2010
186-Gene Signature in Cancer Stem Cells Predicts Recurrence

Stanford University School of Medicine researchers found 186 genes that together can predict the risk of recurrence in breast cancer patients. These genes identified in cancer stem cells found inside a tumor also predict the recurrence of prostate cancer, lung cancer and medulloblastoma.

“These data suggest that there are some fundamental properties of the malignancy that are shared between many types of tumors,” explained Michael Clarke, MD, the Karel H. and Avice N. Beekhuis professor in cancer biology. Dr. Clarke is also the lead author of the study, which is published in the January 18 issue of the New England Journal of Medicine.

Dr. Clarke also found that coupling this 186-gene signature with a second group of genes implicated in normal cells  surrounding the tumor, called stromal cells, one can predict aggressive cancers with an even greater accuracy. Patrick Brown, PhD, professor of biochemistry, previously discovered these genes. Dr. Clarke said the finding shows that malignancy is the result of an interaction between the cancer cells in the tumor and the environment, as many researchers had previously surmised.

Dr. Clarke and his team identified the genetic pattern in breast cancer stem cells taken from tumors and verified the results in a standard tumor biopsy containing a range of cell types. That same biopsy can also remove the stromal cells that are needed for the second genetic profile.

“This paper demonstrates, for the first time, the clinical value of isolating pure human cancer stem cells,” pointed out Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Medicine, who was not involved in the study. “Mike Clarke and his colleagues have now shown that the human breast cancer stem cell reveals information not evident when the whole tumor is analyzed. We plan to incorporate these findings in our approaches to the care of cancer patients, starting here at Stanford.”

Dr. Clarke has begun working with surgeons on tools to assess the best treatment for each patient. For example, he hopes that within five years, if a patient’s genetic profile implies that her tumor is unlikely to return, a surgeon will be able to leave more breast tissue intact.

Over time, Dr. Clarke said, researchers will likely be able to refine the list of genes needed to most accurately determine a patient’s risk of recurrence. Such a shorter list of genes could make a genetic profiling test more cost-effective for widespread use.

Clarke found the first cancer stem cell in a solid tumor in 2003 while at the University of Michigan. Previously, researchers thought these cells were restricted to blood cancers. Since then, other researchers have found them in brain, prostate as well as head and neck cancers.

Other Stanford researchers who contributed to this study include Piero Dalerba, MD, postdoctoral scholar, and Gavin Sherlock, PhD, assistant professor of genetics. This work was supported by grants from the National Cancer Institute, the Breast Cancer Research Foundation and the Virginia and D.K. Ludwig Foundation.

                                                                                                                                                                                                —Querida Anderson

National Prostate Cancer Coalition Commences Clinical Trial Education Program

The National Prostate Cancer Coalition (NPCC) launched a program to educate men with prostate cancer about the possibility of entering relevant clinical trials. “We’re conducting our “Get in the G.A.M.E. -Get All Men Educated” initiative because a recent survey of prostate cancer patients shows that only a very small percentage of patients—about 12 percent of men with prostate cancer—know that clinical trials are an option,” explained Richard N. Atkins, MD, NPCC CEO.

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