Wednesday, August 1, 2012
Several independent studies have provided strong evidence for the existence of cancer stem cells in some brain tumors, and potentially in skin and colon cancers as well. Like their powerful, healthy counterparts, the putative cancer stem cells have the ability to endlessly self-renew and produce progeny that can develop into all the different types of cells within a tumor. Some may even be resistant to many standard cancer therapies, and could be the cause of cancer relapse. But whether they actually exist in solid tumors is a controversial notion. Three studies published today won't end the debate, but they do lend greater credence to the theory, and could provide support for new approaches to cancer treatment.
Cancer stem cells are controversial partly because the experiments suggesting their existence have yielded inconsistent results. Experts say that could be due to the methods used to study them. Today's studies take advantage of imaging techniques that let researchers trace the fate of a cell and its progeny within a single mouse. All three groups looked at models of skin, brain, and colon cancer, and each study yielded varying degrees of support for cancer stem cells. The results suggest that at least some solid tumors carry the powerful cells, which may require special attention during cancer treatment.
"Cancer stem cells might explain why certain tumors might come back after treatment," says Hugo Snippert, a cancer biologist at the University Medical Center Utrecht in the Netherlands and an author of one of the studies. "You can imagine if you get rid of the whole tumor except for one cancer stem cell, then the cancer stem cell fuels a new tumor, and you get back to original scenario," he says.
But it doesn't make sense to attack cancer stem cells alone, says Snippert. One of the mysteries of this cell type is its origin. Such cells could be deranged forms of normal stem cells in the body, or they could arise from other cell types that gain the stem-like abilities, which suggests that non-stem cells within a tumor could transform into the dangerous subtype. "If you follow and accept that line of argument," says Robert Weinberg, a cancer biologist at the Massachusetts Institute of Technology who was not involved in today's studies, you then need to eliminate both the stem cells and non-stem cells in the tumors.
While two of the reports looked at early-stage, largely benign tumors, a third report from Luis Parada's group at the University of Texas Southwestern Medical Center in Dallas studied deadly brain cancers called gliomas. They found that following chemotherapy, a subpopulation of cells with stem cell-like properties survived and seemed to instigate new tumor growth. They did this by producing a transient population of highly proliferative cells, which set up the hierarchy of cancerous cell types in a tumor.
If this subpopulation exists for a significant proportion of solid tumors, it will have a profound impact on how to treat and monitor cancers, says Parada. "If the cancer stem cell model is true, then assessing the efficacy of the therapy by tumor size or shrinkage would be less relevant, because what would really matter would be the effect of any therapy on the cancer stem cell population," he says.
While the cancer stem cell model may not be accepted as truth in all corners—even with these three studies—the possibility of the existence of such cells has prompted some groups to find ways to seek and destroy them. One such group is Boston-area Verastem, a company cofounded by Weinberg. Verastem is developing tools to specifically monitor them, and is designing drugs to selectively decrease cancer stem cell numbers. The company says several of its experimental models indicate that cancer stem cells resist standard treatments, but can be selectively destroyed by its three lead drug candidates.
Sean Morrison, a stem-cell biologist at the University of Texas Southwestern Medical Center who was not involved in today's studies, says the papers "offer varying degrees of support that in at least certain kinds of tumors, there really are subpopulations of tumor cells that are responsible for tumor growth. The important question for the field is what fraction of cancers fall into each: is it really only a minority of malignancies that follow the cancer stem cell model, or are there many malignancies that follow the model? Nobody knows."