Talk:Carcinogenesis

Structure

Well, it's a good thing that this article is a MCOTW, because it sure needs a lot of work. I'd like to hear people's ideas about how to structure this article, since we don't have a neat template for this sort of topic, like we would for a disease. This is a very rough idea of a structure just off the top of my head. Feel free to tear it apart:

Introduction - layman's definition of the process, summary of causes leading to oncogenesis
Properties of malignant cells

Highlight the differences between malignant and normal cells, and how this can lead to disease and death

Include scanning electron micrograph of transformed cancerous cell vs. normal cell

Mechanisms of carcinogenesis

Basic genetic mechanisms - two hit hypothesis

Discussion of oncogenes and tumor suppressor genes

Basic overview of normal cell cycle control, and how this is disrupted in cancer.

How much detail? The amount of research on this is staggering.

This section could use a nice clear schematic illustrating the "two hit" hypothesis.

Causes of carcinogenesis

Discussion of factors that can contribute to cancer: random mutation from DNA synthesis (cancer occurs more often in frequently dividing cells), carcinogenic chemicals, diet, ultraviolet light, etc. etc.

This is an important section to get down right. There are many, many myths out there.

Current research

A more dynamic section, pretty flexible

Let me know what you think. Mr.Bip 00:44, 17 August 2005 (UTC)[reply]

P.S. I have to run soon, so I don't have time to pore through this, but here are many many useful images available for free use from the NIH: Visuals Online - National Cancer Institute

That's a great source! On the images front, we probably ought to have some histology images; one or more illustrative H&E sections would be great. Ideally I'd suggest a normal section for comparison, plus something aggresive and a carcinoma in situ to show different degrees of invasiveness. TenOfAllTrades(talk) 02:25, 17 August 2005 (UTC)[reply]

Jellytussle's comments about evolution and cancer bring into focus the central importance of microevolution to cancer. Jellytussle also describes some minor aspects of the massive experimental support for microevolution in cancer.

However, I do not understand the introduction of Linus Pauling and the attack on orthomolecular medicine. What has this to do with a new scientific hypothesis about the nature and cause of cancer?

The microevolutionary model is conventional biology. It synthesises the known scientific facts and experimental data into a neat description. For experimental support look to the existing base of conventional scientific data. It is consistent with current and conventional scientific ideas.

I ask anyone with an open mind to read Jfdwolf's comments and come to their own conclusions. I said this has the appearence of censorship in that the deletion of the article is based on openly admitted bias.

Leave microevolution out but the remaining article is now out of date and misleading. Lentof

Um, the theory isn't being opposed based on lack of experimental evidence. The initial posters of this material asserted that it was some newfound theory as though 2005 was some Eureka moment for cancer. On the contrary, we could easily accommodate all this material, provided that these two authors don't get credit for merely being Captains of Obviousness. Jfdwolf removed the text on the basis of the supposed narrow authorship of the theory. Can you clarify that the proposal of the book and the standard accepted clonal evolutionary model of oncology is the same? Then, we can use the material, just not elevate the two authors to fantastic heights. -- Natalinasmpf 18:59, 29 December 2005 (UTC)[reply]

References

The article could do with a few references, although most information is just an amalgam of what can be gleaned from textbooks and other resources. Are there any original/classical references we ought to cite? JFW | T@lk 00:27, 18 August 2005 (UTC)[reply]

Added some references, mainly reviews. --WS 17:59, 28 August 2005 (UTC)[reply]

Microevolutionary model

The model sounds reasonable, but I am very suspicious of the reference, which contains the word "ascorbate", which sets off my orthomolecular alarm bells.[1] JFW | T@lk 08:23, 28 December 2005 (UTC)[reply]

It is difficult to convey how shocking I find it, that a physician should make such a prejudiced statement so openly. Paraphrasing, it sounds as though the writer is saying: “The science looks fine to me, but it contains a reference to vitamin C and should therefore be considered for deletion.” I do not know what an “orthomolecular alarm bell” is, but it certainly has a POV. Lentof

Please give me a good reason not to be extremely weary of the orthomolecular mafia. I'm allowed to express my POV on talk pages, and will certainly continue doing so. JFW | T@lk 16:49, 29 December 2005 (UTC)[reply]

I am a bit suspicious of this too. I have three issues: the use of "alternate theory", as opposed to an alternate standing somewhere in the carcinogenic line in the traditional field of oncology. Two, it's based around one book, released this year, and there might either be OR (just a bit) - or more of NPOV problems, ie. because as a new "alternate theory" one must consider credibility in terms of representation. Thirdly, is it really any different from the currently accepted theory of clonal evolution? Is this any new? -- Natalinasmpf 06:16, 29 December 2005 (UTC)[reply]

The entry, which describes cancer as microevolution to a new "species" of "selfish cell", is in the public interest. Clonal evolution, as previously described, differs from microevolution as it does not have the same degree of explanatory power. It does not, for example, incorporate the redox signalling, resultant biodiversity, the aneuploid onset of malignant form, or make the same predictions.

The microevolutionary model is a hypothesis rather than a theory. It is an alternative explanation to the current ideas but is entirely consistent with current models and data. Microevolution provides an overview that makes specific, scientifically testable predictions. Lentof

Checked google - [2] - sounds like a rational treatise, but only gets so many hits. I am suspicious. -- Natalinasmpf 06:25, 29 December 2005 (UTC)[reply]

I've taken it out. JFW | T@lk 08:53, 29 December 2005 (UTC)[reply]

On what grounds has this been removed? Are they scientific or because of your current POV? How is this to be explained? On the topic of orthomolecular medicine, did you see Dr Abram Hoffer’s comment on the back of the book (which I am certain you must have read) –

They call their hypothesis the microevolutionary hypothesis of cancer. It is so simple and so elegant; I wish I had thought of it first.”

Lentof

So simple and so elegant that the only support we have is one book written by two people. The paradigm presently used by cancer scientists is the work of thousands of researchers. And suddenly two people come crashing on the scene and expect their hypothesis to get equal coverage? JFW | T@lk 16:47, 29 December 2005 (UTC)[reply]

The article itself needs to be taken care of. IMO, it's legitimate material, it just either needs to be reintegrated to existing topics and/or shortened for NPOV reasons. -- Natalinasmpf 09:30, 29 December 2005 (UTC)[reply]

The consensus is that the material is legitimate but differs from the current paradigm. The problem appears to be the POV of the detractors. The material is a rather bland explanation of the miroevolutionary model and has NPOV except that it differs from previous ideas. Lentof

Lentof, see my response above. A hypothesis advanced by two people in a book is not to be placed on equal footing with the work of 1000s of research scientists, especially if there is not even experimental support. I agree it sounds fascinating, but that does not make it notable. JFW | T@lk 16:47, 29 December 2005 (UTC)[reply]

My answer is here. JFW | T@lk 16:51, 29 December 2005 (UTC)[reply]

I am aware of three facts:

Jfdwolf is openly biased against a branch of medicine
There is an abundance of scientific evidence supporting this model
Jfdwolf has not read the book

Overt predudice has no place in Wikipedia. This has the appearence of censorship. Lentof

Lentof, orthomolecular medicine (OMM) is not a branch of medicine. It is a form of alternative medicine. The "scientific evidence" procured by OMM is not accepted by mainstream medicine. I have indeed not read the book nor do I care to; the fact is that you are inserting unaccepted theories under the guise of mainstream science.

Look, I can elicit the "censorship" response within 24 hours! Jfdwolff's law has been confirmed experimentally. JFW | T@lk 17:54, 29 December 2005 (UTC)[reply]

Two main points.

Firstly, orthomolecular medicine, both in theory and practice falls well outside the mainstream of conventional cancer biology and oncology. It does not have an evidence base that is acceptable by conventional standards: most of it is based on anecdote. Adding Linus Pauling's name to the equation is not helpful in this respect. Orthomolecular medicine belongs in the section on Alternative medicine.

Secondly, it is widely accepted that there is selective pressure on tumour cells both from the host body and from treatments such as chemo and radiotherapy. Those cancer cells which survive initial treatment are likely to be the ones with traits which make them more resistant; these daughter cells are likely to be the ones which repopulate any recurrent disease. This is one explanation why recurrent or relapsed disease is less likely to respond again to first line treatment, and this is why different (second line) chemotherapy is often used in this situation. Some cell lineages may also be intrinsically genetically unstable, throwing off natural mutants. This can cause a step-wise increase in cell dysplasia, and is commonly cited as the explanation for the evolution of colonic polyps into frank carcinoma. It is also a reason why some indolent tumours suddenly appear to transform or upgrade into much more aggressive disease.

This article on carcinogenesis should discuss the maintream views and hypotheses on the subject. There is no reason why alternative and unconventional explanations should not exist on another page which is clearly labelled as such.Jellytussle 17:59, 29 December 2005 (UTC)[reply]

So which is it?

I don't get even how this is new. We do have a red link for clonal evolution, the evolutionary theory of cancer which has been accepted at least a decade (but we don't have an article for). This is what confuses me: as some newfound research, it needs to be played down, as part of a neutral point of view policy. I don't think the theory has any "detractors", if any, the theory is not even new. Three things:

Either the theory is not really new, and has to be reintegrated into the rest of the text
The theory is a new-build up onto decades of research into a particular track, ie. it's compatible with current models
The theory is new and incompatible with the previous evolutionary model of cancer, perhaps legitimate but has to be shortened so as not to overwhelm the classical

(We're leaving out any allegations of fringe science ie. that is found in aetherometry, because I'll assume good faith at the moment).

Which are you arguing for? Alternative theories can be represented, but they must be represented neutrally. If it's just a mainstream development, then it has to be reintegrated and/or the existing article on microevolutionary models can be adapted to other evolutionary models of cancer. This has a very good chance of being reintroduced, as long as no one claims a huge chunk of normally accepted scientific facts (ie. that free radicals and reactive oxidants cause cancer, et al. are all due to two people writing a book, no matter how brilliant.

For example: "Most notably, it allows the various different types of cancer to be viewed, not as separate diseases with different causes and cures, but as the results of a common process, with the obvious advantage that this gives in the search for treatments." - One would think this obvious. Why do the authors think these are new developments? Treating the morphology of cancer cells like microevolution within the human body is not a new theory. Perhaps they developed some of it.

What would be a new development would be applying this theory into practical use - cancer cells compete with each other. If one wants to be Machiavellian and play biological politics with the cells, use them to destroy each other (the enemy of my enemy...) That would be a new development. Wasn't the evolutionary model of cancer proposed decades ago, and has been refined till now? What's new? -- Natalinasmpf -- Natalinasmpf 18:09, 29 December 2005 (UTC)[reply]

The warm approval from an orthomolecular figurehead and the shouting of the refrain "vitamin C" after every stanza is enough to make me think this is not to be seen as mainstream medicine. It's a rephrasing of the principle of clonal evolution, but sprinkled with Pauling, Rath and vitamin C. JFW | T@lk 18:15, 29 December 2005 (UTC)[reply]

That is true, Vitamin C is indeed a powerful weapon (as is E); but of course there comes a point where taking any more doses would be ineffective. I mean, it's basically stating the obvious, sort of like, "eat more foods with fibre" like a magic weapon against colon cancer. One can't of course, prevent it entirely, but then I would suppose that would just make the authors Captain Obvious rather than say, non-mainstream. -- Natalinasmpf 18:22, 29 December 2005 (UTC)[reply]

Exactly right—the microevolutionary model is just a recasting of the clonal evolution model, with a dash of vitamin C and niacin tossed in. While antioxidants may (modestly) reduce the risk of developing cancer in the first place, there isn't any compelling evidence to support to notion that they can trigger remission or cure. We would be doing a disservice to our readers to represent that idea as anything but fringe science. TenOfAllTrades(talk) 18:28, 29 December 2005 (UTC)[reply]

I do suppose we could move that microevolutionary model to clonal evolution and just adapt it to our purposes, using the existing material that is commonly accepted, and just modifying the entire "omg, it's new and revolutionary!" attitude it seems to portray, ie. the mention of the book/authors, or anything supposedly "new" about the evolution of cancer. -- Natalinasmpf 19:01, 29 December 2005 (UTC)[reply]

The microevolutionary model has very little in common with clonal evolution. Surely clonal evolution involves changes in a clone of cells while the new model deals with biodiversity and speciation? The word microevolutionary is used in its wider biological context. I thought the aim was to place cancer where it belongs at the center of biological science. The microevolution model actually predicts that while antioxidants will help prevent the proliferation that leads to malignant cancer, most antioxidants will be unhelpful with advanced disease. Ever heard of futile redox cycling or the drug metoxefin gadolinium? Lentof

Prevention being better than cure is pretty obvious, considering that anti-oxidants should be used to prevent DNA damage, not cure DNA damage. I don't see the difference between clonal evolutionary and microevolutionary models of cancer (and I recall correctly, microevolution is involved in clonal evolution). Clonal evolution predicts that natural selection will allow cancer to diversify, and eventually "select" the cancer that can feed itself more (angiogenesis), last longer (production of telomerase) through mutations allows normal cells to evolve into cancer cells within a lifespan due to evolution, and selection pressures create certain morphology mechanisms of preferring certain cancer cells with certain traits. If this is truly a "new theory", it has yet to provide any new solution to anything based on evolutionary mechanics - ie. using the fact that different microspecies of cancer cells compete with each other in the principle of "the enemy of my enemy". Emphasising antioxidants is not a unique feature of this new theory - preventing DNA damage before it happens is a common sense philosophy ever since the origins of cancer was discovered. (Oh by the way, those with Glucose-6-phosphate dehydrogenase deficiency can't take Vitamin K supplements or its derivatives, I suppose that poses an obstacle to this seemingly "magic bullet" treatment). -- Natalinasmpf 20:57, 29 December 2005 (UTC)[reply]

The microevolutionary model is not a treatment but a model. However, it predicts which treatments are likely to be effective. For example it predicts that there are numerous substances with low toxicity that will selectively kill cancer cells. It predicts that there must be even larger numbers of substances that will inhibit the growth of pre-malignant cells and that these differ from those that destroy malignant cells. This is predicted from the requirements for evolution of multicellular forms. It is an example of one of many predictions not derivable from clonal evolution. A brief search of Pubmed will supply a large (and generally ignored) dataset confirming these predictions.

Consider the biological context. Since the first multicellular organisms evolved they have been in danger from the growth of aberrant cells. So for hundreds of millions of years there has been selection pressure for non toxic substances that will prevent, inhibit or destroy cancer.

An interaction between vitamin K and glucose-6-phosphate dehydrogenase deficiency has little significance for the model or the treatments that are predicted to be effective.

The primary action of antioxidants in preventing development of cancer does not depend on "DNA damage". The first action is prevention of proliferation by cell signalling and inducing a reducing redox state of the cell. Check out redox signalling rather than mutations. Ask yourself how oncogenes and tumor suppressor genes actually work at the biochemical level.

The microevolution model specifies that the defining characteristic separating pre-malignant from malignant cells is gross changes to the genome and specifically aneuploidy. Has anyone ever seen a non aneuploid malignant cancer?

The premise is cancer is fully explained by microevolution. You can apply standard methods of population dynamics, biodiversity studies and evolutionary methods to cancer. An example is when the process of metastases is described in terms of island biogeography and biodiversity; the position, growth rates and late recurrence of secondary growths can be explained. When this is done, the process is seen as basic biology not a confusing branch of medicine.

The word microevolution may be making you think small. Imagine the whole sciences of evolutionary biology and ecology are applied to cancer. The result might be described as microevolution, but it is most definitely not development of a clone of cells with mutation damage to the genes. User - TONS.

First thing, I do not like your condescending language. I am not at all distracted by the use of the term "microevolutionary", as I came across it before I even heard of this book, in the context of clonal evolution. It is my opinion that whatever discovery is made is either a buildup of existing research, ie. not revolutionary, but if not, then the problem would be - vetting against original research. Firstly, give me those PubMed citations please. My real concern is how this entire thing is disjunct from the other articles, and does not integrate its concepts well, even as an alternate point of view. Ie. integration shouldn't be simply tacking on a section, but whatever section is implemented should have brief lead-ins beforehand. -- Natalinasmpf 02:13, 30 December 2005 (UTC)[reply]

TONS wrote, "The microevolution model specifies that the defining characteristic separating pre-malignant from malignant cells is gross changes to the genome and specifically aneuploidy. Has anyone ever seen a non aneuploid malignant cancer?"

Well erm, YES. Many of the classic genetic alterations in cancer cells are small mutations: deletions, amplifications, base substitutions in otherwise normal diploid cells. These cannot be detected by classical cytogenetics, and may require FISH for correct diagnosis. Aneuploidy has no relevance in this situation.Jellytussle 03:18, 30 December 2005 (UTC)[reply]

TONS wrote,"Consider the biological context. Since the first multicellular organisms evolved they have been in danger from the growth of aberrant cells. So for hundreds of millions of years there has been selection pressure for non toxic substances that will prevent, inhibit or destroy cancer."

Danger from aberrant growth of cells, yes. But the next contention is wrong. There has been selection pressure for intracellular defence and repair mechanisms, of which there are a multitude (cell cycle arrest, apoptosis, various DNA repair mechanisms etc.), and for extracellular mechanisms (the immune system.) Non-toxicity has nothing to do with it.

"The premise is cancer is fully explained by microevolution. You can apply standard methods of population dynamics, biodiversity studies and evolutionary methods to cancer. An example is when the process of metastases is described in terms of island biogeography and biodiversity; the position, growth rates and late recurrence of secondary growths can be explained. When this is done, the process is seen as basic biology not a confusing branch of medicine."

This is confusion of an analogy with a homology.Jellytussle 05:04, 30 December 2005 (UTC)[reply]