Why Tumors Won’t Die

Pediatric brain surgeon Peter Dirks of the Hospital for Sick Children in Toronto remembers well the cancers that have evaded his knife, withstood chemotherapy and radiation, and somehow reemerged to end a patient’s life. Now he and Michael Clarke of the University of Michigan Medical School say they have learned the secret to cancer’s tenacity: a cluster of mutant stem cells that continuously regenerates tumors. Their discovery could lead to a powerful new therapeutic approach, one that targets the source of the disease, spares healthy tissue, and may even knock out brain cancer for good.


Stem cells can replicate indefinitely and give rise to more than 200 kinds of tissue types found in the human body. So-called cancer stem cells are thought to work in the same way, cranking out diseased tissue types instead of healthy ones. Although scientists first isolated cancer stem cells in the early 1990s, Dirks and his group are the first to show that the cells can rebirth entire brain tumors inside a living animal.


In their study, investigators extracted cancer stem cells from human brain-tumor
tissue and injected about 100 of them into the brains of healthy mice. The cells, which were tagged with a fluorescent marker, sprouted clones of the original human tumors. Researchers injected up to 100,000 non-stem-cell cancer types as well, but in all those cases, the mice brains remained tumor-free. What’s more, Dirks noticed that aggressive brain-tumor types contained the most stem cells, suggesting that the number of stem cells in a tumor might predict a
cancer’s severity.


Dirks says that the ultimate goal is to develop a therapy that targets cancer stem cells. But first he and his team must identify a marker that can better distinguish healthy stem cells from rogue ones (the protein tagged in the study is native to both).


In the meantime, he hopes to use the mice bearing human tumors to personalize cancer treatment, determining which therapy is likely to work best before prescribing it to a patient.