Cancer researchers can sequence tumor cells’ genomes, scan them for strange gene activity, profile their contents for telltale proteins and study their growth in laboratory dishes. What they have not been able to do is track errant cells doing what is more relevant to patients: forming tumors. Now three groups studying tumors in mice have done exactly that. Their results support the ideas that a small subset of cells drives tumor growth and that curing cancer may require those cells to be eliminated. Instead of testing whether a therapy shrinks a tumour, for instance, researchers would assess whether it kills the right sorts of cell.
All three research groups tried to address this knowledge gap by using genetic techniques to track cells. Parada and his co-workers began by testing whether a genetic marker that labels healthy adult neural stem cells but not their more specialized descendents might also label cancer stem cells in glioblastoma, a type of brain cancer. When they did so, they found that all tumors contained at least a few labelled cells — presumably stem cells. Tumors also contained many unlabelled cells. The unlabelled cells could be killed with standard chemotherapy, but the tumours quickly returned. Further experiments showed that the unlabelled cells originated from labelled predecessors. When chemotherapy was paired with a genetic trick to suppress the labelled cells, Parada says, the tumors shrank back into “residual vestiges” that did not resemble glioblastoma.
The papers provide clear experimental evidence that cancer stem cells exist, says Robert Weinberg, a cancer researcher at the Whitehead Institute in Cambridge, Massachusetts. “They have made a major contribution to validating the concept of cancer stem cells,” he says. But cancer cells probably also act in more complex ways than those observed, he warns. For example, non-stem cells within the tumor might de-differentiate into stem cells.
The next step, the three groups say, is figuring out how the cells tracked in these experiments relate to putative cancer stem cells identified by years of transplantation studies. Researchers are already busy hunting for ways to kill these cells; now they have more tools to tell whether such a strategy will work.
Via Dr. Stefan Gruenwald