Emphasis on cancer stem cells grows with recruitment of second top scientist
BY AMY ADAMS

As Philip Beachy, PhD, moves his lab from Johns Hopkins University to the Stanford School of Medicine, he brings an additional piece to a puzzle that lies at the heart of the school's cancer research efforts: What is the role of cancer stem cells in the disease's progression?

Beachy, whose work has advanced the study of the molecular pathways used by cancer stem cells and cells in the developing embryo, became professor of developmental biology on Sept. 1. He follows last year's arrival from the University of Michigan of Michael Clarke, MD, who first identified solid tumor stem cells in breast cancer in 2003.

With the addition of Beachy and Clarke, Stanford has taken another step toward cementing its position as a leader in a field that is quickly gaining widespread acceptance. Recent reviews in both the New England Journal of Medicine and Nature tout cancer stem cell research as a likely source of future cancer treatments. True, some researchers question the cells' significance. But a consensus seems to be building that knowledge about these cells will play a pivotal role in developing better ways to combat the disease.

Cancer stem cells are believed to be the cells that continuously replenish cancer, like the spring at the source of a creek. Only the cancer stem cell can form a new cancer. The regular cancer cells, which arise each time the cancer stem cell divides, cause damage by their sheer bulk, yet they alone can't form a new cancer.

Because of the cells' apparent role in cancer, Irving Weissman, MD, who leads both the Stanford Institute for Stem Cell Biology and Regenerative Medicine and the Stanford Comprehensive Cancer Center, has made cancer and leukemia stem cells a primary focus of the school's expanding effort to treat cancer and develop new therapies. He and others believe the reason many cancers return after treatment is that radiation and most forms of chemotherapy kill the quickly dividing cells but leave a significant fraction of the cancer stem cells unharmed. Completely eliminating a cancer means eradicating its stem cells.

"The overall plan is to amalgamate the cancer stem cell work with the cancer gene discovery efforts and translate that into clinical trials at Stanford," Weissman said.

Already collaborations to find new cancer stem cells in solid tumors, basic research into how the cells replenish themselves and work to translate that basic science into the clinic are establishing the multidisciplinary research program that will put Stanford at the forefront of the cancer stem cell field.

Pathways to cancer

Beachy didn't start out studying either cancer or stem cells. Instead he received his PhD in biochemistry from Stanford, where he studied the early development of fruitflies. That work led him to focus on the role of a protein called Hedgehog in the developing fly. He has since become one of the foremost experts—along with Matthew Scott, PhD, professor of developmental biology—in understanding how the Hedgehog protein signals cells during the fetal development of such animals as flies, mice and humans. The protein plays a critical role in telling cells where they are in the body and what type of tissue they should become.

As that work progressed during his 18-year career at Johns Hopkins, Beachy realized that the Hedgehog protein signaling pathway also had a role in cancer. Some of his colleagues, including Scott, had studied mutations in genes coding for proteins that interact with Hedgehog; the researchers found that people with those mutations were at greater risk for several cancers. Beachy found that a drug known to inhibit Hedgehog protein successfully reduced the size of brain tumors in a lab dish and in mice. In later lab experiments, that same drug effectively inhibited the growth of cells from cancers of the lung, gastrointestinal tract and prostate. Several pharmaceutical companies are now exploring the use of such drugs to treat human cancers.

Hedgehog appears to encourage the cancer stem cell to churn out new cancer cells. Another protein that plays a similar role in some cancer stem cells is Wnt (pronounced "wint"), which is the domain of Roel Nusse, PhD, professor of developmental biology and an expert in Wnt signaling. "Hedgehog and Wnt are really sister pathways that may be fairly fundamental in many types of cancer," said Beachy, who is also a Howard Hughes Medical Institute investigator.

Weissman said that work by Beachy, Scott and Nusse dissecting how Wnt, Hedgehog and other proteins maintain cancer and leukemia stem cells could result in drugs that interfere with those pathways, eliminating those cells.

If such drugs do come out of their research, both Weissman and Beverly Mitchell, MD, cancer center deputy director, want to have the trials also take place here to benefit Stanford patients.

Beachy shares that goal. One of the reasons he chose to move to Stanford is its emphasis on basic research that could yield new therapeutic approaches, in addition to the chance to work with other experts in his field.

Read more here:

http://news-service.stanford.edu/news/2006/september27/med-beachy-092706.html