Dna Cancer Basis

Discussion of possible causes of cancer.

Background: Unusual characteristics of tumor cells:

This might be a good place to insert the recent hypothesis that cancers, all cancers, have their roots in chromosomal damage and that a generic treatment for cancer (a genuine 'cure for cancer') can indeed be developed. This would be a far cry from the current fragmentation of research and treatment efforts.

Another hypothesis rotates that view 90 degrees: that all cancer is caused by viruses, exacerbated by damage to genetic structures that would otherwise assist in resisting the virus. Prototypical tumors have characteristics that match many of those on the usual attempts at checklists of what defines "life".

If you look at the list of characteristics of tumor cells I added to the top of the page, it is immediately evident that every single one of those characteristics is highly functional, as if the tumor cells were carefully designed to spread, as if they were a separate organism from (or parasite on) the host.

It is patently absurd to suppose that such wonderful design, in toto, should seriously be considered "damage". A damaged cell tends to function worse than before. These cancer cells are functioning better than before - albeit at a cost to the host organism.

hmm... Is there any evidence for that hypothesis? As far as I know, there is no evidence for cancers being caused by viruses. The best current evidence suggests that cancers are cellular reproduction processes gone haywire, as opposed to cellular reproduction taken over by a virus (or other foreign organism). Viruses could cause this indirectly, by inserting themselves into genes at inopportune places. For example, if a virus inserts itself in a gene coding for DNA repair, it can cause DNA repair to go faulty. The damage caused to cellular reproduction in this manner is no different from any other damage to cells. -- AlexAusch?

Person2: 'Cellular reproduction mechanisms gone haywire' is the definition of cancer, not its actual cause. At least, not for researchers trying to look beyond Cancer 1234-B. There's plenty of evidence for cancers being caused by viruses, though I don't know how general that is.

Could you point me to some of this evidence? The only evidence I've seen was for a non cause-effect type relationship. I've read some about this, and all that I've read suggests that, when it happens that a virus is the ultimate cause for cancer in a specific patient, it's like a case of a straw breaking the camel's back. That is: (1) the virus isn't cancer causing, but has some other effect, which, accumulated with other DNA damage, causes cancer (2) if the virus wasn't going to do it, something else would have - the type of damage caused by the virus can be caused by a large variety of factors (radiation, certain chemicals, etc...)

This means that preventing the viral infection will not prevent the cancer from happening, it will only slow down its progress. (ie, it's not a direct cause-effect relationship, but a probabilistic one. Certain types of viruses cause DNA damage, and thus increase the probability of cancer occurrence. This is a weaker statement than the statement: certain types of viruses cause cancer. And it's even weaker than saying: certain viruses cause cancer). -- AlexAusch?

No; you are speculating (although I think that was by far the majority speculation 3 decades ago), but I think that evidence is overwhelming in the other direction now. See my above comment about tumors fitting the definition of life; that practically makes the link derivable from first principles (not that anything in biology is susceptible to that. ;-) -- DougMerritt

Not if a part of a living thing can become an independent organism, the suggested origin of tumors and viruses alike.

The case of papilloma virus and its involvement in cervical cancer is interesting. The virus doesn't directly damage DNA by itself but it encodes for two proteins (E6 and E7) which find the cell's master cell-cycle control protein p53 and target it for protein-mediated destruction. Thus, even though the infected cells are genotypically p53+/+, they are phenotypically p53 negative. This puts the infected cervical cells into a hyper-proliferative state (which helps the virus divide). At this point the cells are pre-cancerous, but not actually cancerous since they still can't grow in crowded conditions and can't detach to metastasize throughout the body. They show up nicely on a pap-smear and can be removed either surgically or with laser treatment. If not removed, they become susceptible to picking up the additional chromosomal mutations that transform them from pre-cancerous to cancerous although it is by no means certain that they will make this transition, which is to say that not all people with an untreated cervical papilloma infection will develop cervical cancer, just significantly more than a matched set of uninfected people would. The HeLa? cell line was established in 1951 from the cervical cancer cells of a patient who later died of the disease (31-year-old Henrietta Lacks - dies 8 months post-diagnosis). These cells are still in culture and going strong today. They don't have infectious papillomavirus in them anymore, but they still do have the viral E6 and E7 proteins, now encoded on genes integrated into the main chromosomes of the cells themselves rather than in a freestanding viral genome. In recent years several people have used RNA-interference to shut down the expression of the E6 and E7 genes and oddly enough this appears to reverse the cancer-phenotype of these cells. They slow down, stop dividing and eventually just die on their own. This despite over 50 years of in vitro culturing opportunities to pick up additional growth-promoting mutations.

Interesting. But I wouldn't call that "oddly enough"; this seems compatible with viral origin theories.

Well certainly Henrietta Lack's cancer was viral in origin. The "oddly enough" part is that in general inactivation of p53 alone is insufficient to transform a cell to a cancerous state so the reactivation of p53 would seem unlikely to be sufficient to transform the cell back to a non-cancerous state.

To be fair, I can imagine a scenario that sabotages the viral hypothesis I've been defending: one can imagine that tumor cells are behaving similarly to how they did during the first 3/4 of the 4 billion year evolution they've gone through, and that the damage from radiation, poisons, viruses, or whatever, are breaking the evolutionarily-new mechanisms that were causing them to behave symbiotically, so of course they revert to acting independently and/or parasitically.

Ah...in adding this, I see someone mentioned this above, and I missed it earlier.

I don't find that completely believable, though, because too many of their characteristics are indeed evolved parasitic abilities that they would not have had as single celled free organisms. Angiogenesis perhaps being the most dramatic such example. -- dm

How many, and how reliably? If there's a constellation of effects, then it would make simple reversion unlikely. At the moment, though, angiogenesis is the only trait listed here that wouldn't have been present in an amoeba (some of which are very close relatives of animals, e.g. Nuclearia, and some of which are generally free-living but act as successful parasites once inside someone, e.g. Acanthamoeba). If it's something that could be caused by a single hormone, it could be coincidence, especially if it's only present in some cancers. Speaking of which, are we supposing all cancers share an origin from the same virus, and if not, shouldn't they should differences in such traits anyways?

A quick search, btw, suggests something which should have been obvious: that the tumor cells could develop abilities such as angiogenesis by mutation after they become free-agents, and are quickly selected for it. The comment above on stem cells makes good sense, too. Other finds give reasons to suspect the viral cause is flawed - for instance, cells in chemical induced tumors supposedly do not show a common genetic signature, which would be expected were they all infected by a common agent. Figures show up saying that 10-20% of cancers are viral, but there doesn't seem to be too much certainty in those.

Hmm. This is all very interesting and reasonably persuasive. More vague, though; we still need to learn more about differentiation. -- dm

See also: DeoxyriboNucleicAcid

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