Cancer stem cells are today's discovery. But first, it was just Stem Cells, on which there was a huge debate. Stem cells are cells that have the power of regeneration and are responsible for creating a man out of a sperm and an egg, and subsequently maintaining him. No one doubted the presence of these cells, but the fact that embryos were being tampered with created a huge furore. This was, and continues to be, a controversy galore. And after the US, its now UK's turn to become The Righteous and put some ethics in the minds of "those barbarian scientists". EU has not been so high-handed, and it "may" be a good thing...
To know more about what stem cells are and the controversy involved, Click Here

The topic of the post, breathe easy, is not stem cells but cancer stem cells. So we'll leave the huge debate aside and talk about that more.

Well, fortunately or unfortunately, there is no debate about this. Cancer stem cells have been proven to exist time and again, mostly in the recent past. Cancer, first of all, is not necessarily caused by a single gene, there are multiple issues that can lead to cancer generation. But the general reason for its cause is mutations. Mutations that led to cells behaving and dividing normally, to start replicating at a furious rate, in a haphazard fashion to become a benign lump or malignant in nature.

Earlier doctors used to employ chemotherapy to treat cases of benign tumors and some malignant tumors too. Chemotherapy employs use of radiation and drugs that can, with a certain degree of specificity, kill the abnormal cells in cancerous tissue and leave the normal cells unharmed. However, as we all know, chemotherapy has its nuisances too. Again, it is not a foolproof method of cancer treatment, for many cases of tumor relapse started surfacing soon.

This question - Why does a tumor relapse after treatment? - is one of the most pondered medical questions of recent times. The widespread belief was also the most obvious one. That Chemotherapy does not kill all the cells, some remain, which again give rise to tumors. And the cycle goes on continuing till the hassled patient decides to give up his battle for life.

There were many problems associated with the then existing theory of cancer - that it is the replication machinery gone wrong. For example, why was it required to transfer hundreds of tumor cells to normal animal to cause cancer in the latter? If all cells were sick, any one should give rise to cancer.
The second problem was of tumor heterogeneity. Many tumors show a heterogenous composition of cells. Now if a terminally differentiated cell had started multiplying awkwardly, why would it give rise to unrelated cells??
Such questions could not be satisfactorily answered by the existing logic.

Then in 1997 came a ray of hope, from the University of Toronto in the form of the concept of Cancer Stem Cells. Dr.John Dick had been working on this thoery for quite some time, and had in fact, published a paper to that effect in 1994 in Nature, but it was not adequately recognized then. Finally in 1997, Dr.Dick (I'm feeling kinda oglytopsy while writing this name) again published in Nature Medicine with a larger dataset, and this theory came to be formally recognized as the Cancer Stem Cell Theory.

Evidence has accumulated over the years for the presence of cancer stem cells. They have been shown to be present not just in leukemia, but also breast tumors, brain tumors, in lymphomas and in gliomas. It is not that this hypothesis has not gone through any scrutiny, and some people have even generated a mathematical model for the presence of such cells, which come to the same conclusion. Of course, a fine-sounding nd a well-set theory will receive a lot of support from favorable data until someone calls the bluff (Not that anything like that would happen to cancer stem cells, but after all, the theory of black holes also was a very strong one...Hawking made a case debunking his own interpretation of the nature of black holes, and fought to lose a bet! Click on the link above to know more).

So now basically people are trying to understand how to differentiate cancer stem cells from the normal cells and the other cancerous cells in the tumor. There are two hypotheses regarding the role of cancer stem cells, as shown alongside, and this being an infantile field, reports are coming in rapidly from all corners of the globe. For recent reviews and papers on the field, Click Here. If this theory, which has received strong support from many quarters, is correct, then it wont be long before we are able to cure cancers completely. (1) (2) (3)

Source of the pic: Nature, Vol414, 2001, pg 105

One strange thing about these cancer stem cells is the fact that they are able to differentiate into tissues. So they must be following defined pathways of tissue differentiation. People are now looking at these pathways. Also, if the hypothesis that "the stem cell population in a tumor remains constant" is correct, it means these cells, even in the mish-mash of their hypermutated genomes are able to divide and differentiate into one progenitor and one stem cell (as shown below):

Mother Cancer Stem Cell ----> Progenitor cell + Daughter Cancer Stem Cell

and this would be quite an interesting, and queer happening. I mean, letting go of the shyness in replicating (and thus replicating indefinitely) is one thing, having controlled mechanism of differentiation is a different ballgame altogether!!

So, all-in-all, cancer-stem-cell theory seems all set for further takeoff. There is very little chance that the field would fizz out too soon, so be on the lookout for new news!



PS: Michael Crichton's NEXT is a fascinating read, the concepts being stem cells, tissue and gene patenting, law suits, talking parrot and recombinant chimpanzees. The density of plots is high, and I bet, you will not be able to predict how everything's gonna end, till the last 10 pages...Click Here to go to Crichton's official website.