Take some cells from a tough-to-treat tumor, sort them, and inject each fraction into a different immunodeficient mouse, and only a small percentage of those cells will thrive and form tumors.
This sort of experiment illustrates a concept that has been gaining traction within the cancer research community. Tumors contain a diverse mixture of cells, and only a handful of them can bounce back after treatment. That deadly minority can reproduce indefinitely and differentiate into a wide variety of cell types, just like stem cells. And often they express many of the same genes that are active in induced or embryonic stem cells and inactive in mature tissue.
Not all cancers fit seamlessly into this paradigm. Until recently, the hypothesis that stemlike cells are at the root of cancer recurrence was mired in controversy. But in the past few years, a great deal of evidence has shown that it holds true in many types of leukemia, breast cancer, and brain cancer. In these diseases, the proportion of cancer cells with a stemlike character can sometimes be as high as 40%. On the other hand, some cancers don’t contain any cells that exhibit stem cell behavior.
Many of today’s cancer treatments can wipe out the most vulnerable cells in a tumor, but they often leave behind cells with tremendous regenerative ability. It’s like mowing down a field of dandelions but leaving their roots intact, says William Matsui, an oncologist from Johns Hopkins University School of Medicine who studies cancer stem cells. He explains that measuring the shrinkage of tumors is an awful way to gauge the effectiveness of a cancer treatment. Statistics from large-scale studies of cancer patients show little correlation between how much their tumors shrink and how long they live. Instead, Matsui argues, cancer treatments should be evaluated for the ability to prevent relapses.
Many scientists are becoming convinced that targeting cancer stem cells is the key to preventing relapses. But finding drugs with a robust effect on cancer stem cells isn’t easy. Some stem cells are inherently drug resistant because they replicate slowly compared with mature cancer cells and express proteins that pump out or otherwise eliminate small molecules. Even worse, some stem cells can continue replicating even after traditional anticancer drugs shut down their primary cancer-causing mutation.