Posted by: Dan | August 28, 2007

Taking the ‘Stemness’ Out of Cancer Cells

dangerous cells
[click on image for full-size; from Science, v317: 1029-1031.]

From the pages of last week’s Science Magazine comes an article from Jean Marx: Cancer’s Perpetual Source?. Marx explains:

Beginning about 15 years ago, John Dick’s team at the University of Toronto in Canada provided a new clue as to what makes cancer such a formidable foe. They found that only a tiny population of leukemia cells could transmit the cancer from one experimental animal to another. More remarkably, the cells had a property previously seen only in stem cells: the ability to produce an exact copy of themselves each time they divide, thereby maintaining the ability to reproduce in perpetuity. These so-called cancer stem cells, Dick suggested, might be what makes the disease so hard to eradicate with radiation or chemotherapy.

I’ve commented on the stem cell theory of cancer previously, including some of its strengths and weaknesses. And as Marx notes, it is indeed this capacity for self-renewal that is such a threatening trait of non-benign cancer cells, making such cells deadly and the cancer stem cell theory worth some attention.

The neat thing about Marx’s article however is that it addresses some of the prospects for therapeutic approaches directed specifically at these cancer stem cells. Among them – the drug rapamycin, which can help make up for PTEN loss; new drug development for Wnt, Polycomb and sonic hedgehog pathways; screening large chemical libraries against cell cultures; and antibody-directed cytotoxicity, using cancer stem cell markers (like CD44). The interesting prospect (to me) is here:

Even if cancer stem cells can’t be killed or their spread blocked, they might be restrained in another way: by inducing them to lose their “stemness” and differentiate into non-renewing cells.

I’d hazard a guess and say that there are high hopes for that being an effective therapeutic strategy, especially when delivered as a drug cocktail to modulate other pathways critical in cancer – adding these drug targets to the repertoire for customizing chemotherapies to individual patients.

Marx also notes many of the lingering questions, from cancer stem cell skeptics (who I still consider myself in agreement with):

Despite the huge growth in the cancer stem cell field, skeptics remain. One potential problem is that virtually all the work has involved transplanting human cancer cells into immunodeficient mice. This has raised concerns that the experiments do not accurately reflect what happens during cancer development in humans. Indeed, Andreas Strasser and his colleagues at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have recently challenged the idea that only rare cancer stem cells can initiate tumor formation.

Although others share Strasser’s skepticism about cancer stem cells and many uncertainties remain, there is one sure bet. Given the possible importance of cancer stem cells as therapeutic targets, the field will continue to grow. And at least one skeptic has already been convinced. Duke University’s Rich says that he came into the research hoping to disprove the importance of cancer stem cells. Now, he says, “we are very early in studying cancer stem cells, but understanding them may impact the way we diagnose and treat patients in the near future.”

  • Marx, Jean. Cancer’s Perpetual Source? Science 24 August 2007, 317(5841): 1029-1031.

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