Is cancer a cure?

May 27th, 2008 | Published in Cancer biology | View blog reactions

A few days ago, while navigating in TED territory, I stumbled into this talk given by a Princeton sophomore. The main topic of the talk was to present a different view of cancer than the one we are usually accustomed to. While we are used to thinking that cancer is a terrible disease, it would hardly cross our mind that it could be some kind of a cure, or better an attempt to heal parts of our body that are damaged – an attempt that often gets out of control.

Before going on to read the discussion, make sure you watch the talk. Mind you, if you do not want to get to know the sophomore’s family history, I suggest you skip to the ninth minute of the movie.

[If you cannot see the movie, you can watch it here.]

It was quite interesting, wasn’t it? Let me summarize the main points raised in the talk. Eva suggests that cancer might simply be part of a natural response mechanism aimed at repairing tissue damage. Somehow most of our body, according to Eva, has not had enough time to evolve to handle the response perfectly, so when the damage is prolonged, cancer often arises. However, there are tissues in our body, such as skeletal muscle, which are well-adapted to sustaining damage of various kinds, and is therefore able to keep cancer under control by means of either moderating nutrient access to this cancer, or by inducing differentiation of cancer cells in situ. Eva suggests that one day we might be able to use the mechanisms behind the repair system (basically, cancer) to repair tissue AND control the spread of cancerous tissue. In this sense, cancer could almost become a cure, a form of “therapy”, as she calls it.

I am not to extensively criticize her point of view, as there are some obvious issues with it. There seems to be an underlying assumption that cancer stem cells are always normal stem cells recruited to a damaged region of the body for repair purposes, and that only after getting there these cells become cancerous. This is a mistake, from my point of view. It makes perfect sense that there is an accelerated regeneration process in a damaged tissue. Think of the skin: if you cut yourself, now your skin stem cells will have to work harder to produce new cells, so to repair the damage. I am also aware that prolonged inflammation states associated with tissue damaged have been showed to predispose to cancer.

But much cancer does not necessarily happen in response to inflammation states. Lung cancer is a good candidate for the inflammation militia, but what about leukemia? Brain cancer? Breast cancer? It is known that many cancers are caused by a minuscule population of stem-cell-like cells that cause the disease: some of these probably were originally normal stem cells, but there is mounting evidence that at least in some cases, cells that were not stem cells acquire, through a mix of somatic insults and genetic predisposition, a new undifferentiated state – and that “un-differentiation” and proliferation are actually caused by separate mechanisms.

The talk often oversimplifies, but what really struck me is the idea that, indeed, it is very rare to hear of skeletal muscle cancer. In fact, this must be the first time in my life I even hear of the concept! It never crossed my mind, for a moment, how interesting this could get. Eva suggests that, somehow, skeletal muscle tissue can regulate angiogenesis to limit tumor growth. But I think the explanation she offers last is the one that makes more sense: there must be strong differentiation factors, maybe myoD itself, that are limiting tumor growth – so that, even if the original nucleus of stem cells remains, it can only rarely grow to a full-blown metastasis, as all other progenitors rapidly differentiate into muscle cells.

The idea is fascinating, and easily explorable. All you need is test it in immuno-deficient mice using tumor cells from syngeneic mice bearing a visible/otherwise detectable marker. You can look at metastatic frequencies in various tissues and, if really the frequency is significantly lower (and metastases smaller) in skeletal muscle, you could run some FACS and look at the proportion of cancer progenitor cells in the micrometastases versus the normal ones – if her idea is right, you would expect to see very few of them, as well as many differentiated cells originally derived from the tumor.

What intrigues me about all this is manly that the cancer cells are not different in one or two things from the other cells. Their entire behavior is changed – and only some form of powerful “undifferentiating agent” could do that. In cancer research, we often try to look for the “magic molecule”. But I think it is time to start thinking in terms of a system of interactions involving DNA, epigenetic modifications, proteins and the relations (pathways) between them. The whole system defines cellular behavior, and it is this behavior, not just a couple of molecular players, that is actually changed in some key cells when cancer arises.

Thus, although I am skeptical that cancer might be a therapy, the focus on differentiation and changes in cellular behavior are thing to keep working on, as well as watching carefully, in the next years. Especially for those who are working on stem cell therapies – whose most common side effect is…cancer.

Post Scriptum: I have been included in the latest edition of Gene Genie. The main topic of this edition was the inauguration of Google Health, but you will find a lot more related to health in general, and genetics specifically, by reading the Genie hosted over at Highlight Health.