There are a few words in the English language that instigate fear and dread in all who hear them.  One such word is cancer.  Directly or indirectly, nearly all of us have experience with cancer, but our understanding from individual to individual varies greatly. We all certainly know that cancer cells are bad … very bad. They can grow and spread like wildfire, invading blood or lymph channels that carry them throughout the body. In contrast, over the past decade, we have learned how good stem cells can be. They have the ability to self renew; they can multiply into different types of cells; and they proliferate extensively. When we think of stem cells, with these three distinct properties in mind, we envision them moving in to replace heart cells damaged by a heart attack or brain cells lost in a person with dementia. For most, stem cells conjure up images of healing and hope.But what if the properties associated with stem cells were subverted? What if their unique characteristics became associated with those of harmful cancer cells? We would then be forced to confront the idea that not all stem cells are good for the body – and in fact, some are very bad for the body.

That time has come. There is now abundant evidence that in a variety of cancers, including leukemia, breast cancer and brain cancer, a kind of “evil” stem cell does exist.  According to research published in the New England Journal of Medicine, “Biologically distinct and relatively rare populations of ‘tumor-initiating’ cells have been identified … Cells of this type have the capacity for self-renewal, the potential to develop into any cell in the overall tumor population, and theproliferative ability to drive continued expansion of the population of malignant cells.”(1)

These cells, known as cancer stem cells, comprise a small subgroup of the cells in a tumor and are essential to its growth. However, their role within the tumor can vary. In some cases, they are responsible for all the cells that grow in a tumor. They can also give rise to distant spread of the tumor.  And thirdly, they can become islands of drug-resistant cells that cause relapses after chemotherapy-induced remission. To explain this further — we are now beginning to understand that if cancer treatment does not destroy all the cancer stem cells in a tumor, it can re-grow. So even if a person appears to be cancer-free after treatment then later experiences a relapse, this can be explained by the fact that the cancer stem cells have not been completely eliminated.(1)It follows, then, given this new understanding of cancer stem cells, that strategies designed to attack them directly might more effectively defeat cancer itself.

So where do we go from here? According to Irving Weissman, a stem cell researcher from Stanford, the promise of this line of research can only be realized by studying both adult stem cells and embryonic stem cells, which is currently a controversial topic.(2)

But the good news is, we now know the general direction that further research must go. Here are what experts say we must do:

First, it is necessary for scientists to define the function and behavior of normal stem cells, their  physical features and their biological activities. Without this knowledge, a drug designed to destroy cancer stem cells might also destroy the normal stem cell required for an organ’s continued function and human survival.(1)

Second, scientists must define the function and behavior of cancer stem cells so that they might create unique biologic therapies that will put those cells out of business.(1)

Third, scientists must figure out why current therapies that successfully eliminate the bulk of
tumor cells in a cancer fail to reach and eradicate the cancer stem cells1.  What are the properties of these cells that make them uniquely difficult to kill? We’re making progress toward answering this question, thanks to studies of leukemia cancer cells.  Scientists have determined that leukemia cancer cells are often quiescent — that is, they are able to freeze themselves in time and not divide.(3)

Why is this important?  Because many cancer therapies target actively dividing cells with the notion that since cancer cells divide and multiply faster than normal cells, they will be preferentially destroyed.  But in the case of some leukemias, a subset of cancer stem cells divides more slowly at certain times and can therefore survive cancer treatments. This can allow a small base of cells to bounce back from the treatment and then explode with ferocity.(1)

To attack such cells, scientists will need to design treatments that selectively target the cancer stem cells, independent of the cell cycle.1  It will also be important to study and define the proteins produced by these cells because they may be shielding or protecting them from the cancer treatments.(4)And lastly, we know that in some circumstances, normal blood stem cells accelerate aging in response to chemotherapy and radiation while the cancer stem cells for some reason are immune.(5,6)  This means that with each successive treatment, the cancer stem cells may be gaining a competitive advantage. It’s imperative that we gain better understanding of the biologic and clinical consequences of our current therapies and continue to use this knowledge to design new ones.

If there’s anything in this information to ponder, it should be this. One, stem cell biology is critically related to the behavior of human cancers.  Two, the eradication of cancer stem cells will be essential to improving survival rates for people with some cancers.  Three, it is possible that current approaches to therapy in some cancers may be preferentially benefiting those cancers’ stem cells, which mean future therapies must take this into account. And finally, in the future, just wiping out the bulk of a tumor may not be an adequate measure of success.  Rather, we will need to address the core of the problem, which is likely to reside where the cancer stem cells live and thrive.

For Health Commentary, I’m Mike Magee.

References:

1. Jordan CT, Guzman ML, Noble M. Cancer stem cells. N Engl J Med. 2006;355:1253-1261.
http://www.nejm.org/doi/full/10.1056/NEJMra061808
2. Philipkoski K. Cancer Stem Cells Hint at Cure. Wired News. August 11,2004.
http://www.wired.com/news/medtech/1,64549-0.html.
3. Guan Y, Gerhard B, Hogge DE. Detection, isolation, and stimulation of quiescent primitive
leukemic progenitor cells from patients with acute myeloid leukemia. (AML). Blood.
2003;101:3142-9.
http://www.ncbi.nlm.nih.gov/pubmed/12468427
4. Dean M, Fojo T, Bates S. Tumor stem cells and drug resistance. Nat Rev Cancer. 2005;5:275-84.http://www.joplink.net/prev/200903/ref/22-009.html
5. Wang Y, Schulte BA, Larue AC, Ogawa M, Zhou D. Total body irradiation selectively induces murine hematopoietic stem cell senescence. Blood. 2006;107:358-66. http://www.ncbi.nlm.nih.gov/pubmed/16150936
6. Meng A, Wang Y, Van Zant G, Zhou D. Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells. Cancer Res. 2006;63:5414-9.