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)

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)

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)

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)

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

Needs to be better in general. I have added two core refs for multistage genetic alterations (Knudson, Vogelstein) but I have not put put ref numbers in the text as yet. The knudson sentence needs editing, with respect. Also, probably need a general section on suggested reading. I have added the Tannock and Hill text to general refs. This is an internationally recognised textbook of basic cancer science, and should probably be the gold standard for any cancer biology article in Wikipedia. I'm pretty sure that my formatting needs a bit of kind attention.Jellytussle 00:27, 4 January 2006 (UTC)

Hello, i added a "citation needed" to the last paragraph on clonal evolution. The change was done on 10:49, 12 April 2009‎ by 71.74.241.11. A quick search didnt find any article mentioning this, i would be very curious to read it, sounds a little bit weird. Thx. 6.8.2012 — Preceding unsigned comment added by 92.240.234.46 (talk)

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)

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)

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)

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)

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

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)

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)

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)

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

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)

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)

I agree with Jellytussle on this one. The microevolution theory section ought to stay, since it is a hypothesis held by some, but it needs to be made clear that it is a new and unconventional theory. Kerowyn 18:32, 1 January 2006 (UTC)

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)

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)

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)

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)

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)

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)

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)

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)

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)

Self-published books are not legitimate sources for science articles

The entire section is unsourced, thus reverted. --DocJohnny 16:28, 1 January 2006 (UTC)

The source was clearly stated. I've added a clarification, but restored the section again. Stealth Munchkin 16:33, 1 January 2006 (UTC)

A commercial website selling books is not a source. This is a medical article, thus medical journals would be appropriate sources. A non-peer reviewed commercial book by 2 pharmacologists is not an appropriate source for this article. Also, this topic has its own article and the text does not need to be replicated here. --DocJohnny 16:49, 1 January 2006 (UTC)

None of the rest of the article is sourced *at all* - there are three references at the bottom, and that's it. The text in this article does not replicate the text in the article on the subject, and is specifically related to the topic. I can certainly see an argument that the section might be shorter, giving a briefer explanation of the model along with a link to the main article, but can't see an argument for deleting the section altogether.
The only argument for its deletion that has been proposed is that the *URL* of the site selling the book *contains the word ascorbate*, and that this makes it the work of "the orthomolecular mafia" (who this strange group are I don't know - do they perhaps have protection rackets where you must pay up or be subjected to a nutrient-poor diet that will lead to your death of scurvy?).
I am rather ignorant of any politicking around this subject, but have to say that this looks absurd - people saying "The model sounds reasonable," but arguing for the deletion of the material based on the supposed membership of the originators of the model in a non-existent group whose views the deleter disagrees with, and all this extrapolated from a *single word in a URL*, rather than even being based on the work itself? Stealth Munchkin 17:37, 1 January 2006 (UTC)

Stop this revert war immediately. Discuss the changes first. Preferably, this should be done line by line until consensus agrees it is acceptable, especially for a supposedly new theory such as this. -- Elle vécut heureusement _{toujours dorénavant} (Be eudaimonic!) 19:10, 1 January 2006 (UTC)

This has been discussed and there has been *no* reason given for the material to be removed. "It's sourced from a book available from a URL with the word 'ascorbate' in it" is not a reason, and the material was taken out by the unilateral decision of one editor. And making a revert and *then* saying 'stop the revert war' is hardly a reasonable action. If you think it needs rewording, reword it, but *nobody* has given a single good reason why this information should not be in the article. Stealth Munchkin 19:21, 1 January 2006 (UTC)

By "rewording" I would effectively delete entire blocks of sentences that were factually contested or had neutrality problems, because they are contested and someone who knows about this supposedly "new theory" would have to reword it.

Like which sections? No-one here has raised a single factual problem with the section as written Stealth Munchkin 20:51, 1 January 2006 (UTC)

Anyhow, the primary concern is whether this is a new theory at all. The book is not a source because it's not a neutral source:

So you're now saying that a work in which a hypothesis is proposed is not acceptable as a source when writing about that hypothesis? Is the Principia not citable as a source in a discussion of Newtonian mechanics? Perhaps On The Origin Of Species is not a reasonable source in an article on evolution? Stealth Munchkin 20:51, 1 January 2006 (UTC)

ie. I can't make publish a book, make an article about this theory in the book and then cite the book as a source.

Which no-one has done. The book is being cited by people other than the authors. Stealth Munchkin 20:51, 1 January 2006 (UTC)

Rather, there should at least be some journal endorsements of this theory as a whole, not just the individual components of it. The url casts doubt on the source,

Why does the URL cast doubt on the source? Merely because it contains the word 'ascorbate'? That's the only reason given so far. Is 'ascorbate' some sort of magic word that automatically invalidates everyone who uses it? Stealth Munchkin 20:51, 1 January 2006 (UTC)

and yes it is a valid reason if compounded with many other factors, such as the apparent neological assertion of the theory (despite attempts to resolve this by declaring this not as new, which would have allowed material to stay in). -- Elle vécut heureusement _{toujours dorénavant} (Be eudaimonic!) 20:22, 1 January 2006 (UTC)

This sentence doesn't actually make sense.I think you're using the word 'neological' to mean something other than its actual meaning. If you mean 'the assertion that this is a new theory', then yes, that has been asserted, and as far as I am aware (and I am far from an expert in the field, although I have read the book in question, unlike, it seems, those pontificating against the possibility of it containing an iota of truth) it is a new hypothesis, based on older research. As far as I'm aware, Wikipedia doesn't have a policy that states that new discoveries in fields shouldn't be mentioned - in fact that would remove half the point of the site being changeable in real-time as opposed to a paper-based resource. By all means, that section should include wording to point out that it's a new hypothesis and not yet the accepted medical orthodoxy, but the suggestion that it should be removed is absurd.

Again, no-one has raised any objection to any statement in that section, other than ad hominem attacks on Hickey and Roberts based on some notion of an 'orthomolecular Mafia' to which all people who have ever used the word 'ascorbate' belong (do I belong to the orthomolecular Mafia yet? I've used the word several times... do I get a gun?). In fact even those arguing for its removal have said "The model sounds reasonable". Yet this material is being repeatedly deleted. Even the most obviously, ludicrously wrong ideas get brief mentions in the relevant articles, even if only to debunk them. Yet even though no-one has yet come up with a single objection to this material other than "The book it references is available at a URL that mentions ascorbate! The authors must be cranks and heretics and evil bad people and so they cannot possibly have anything worth saying! No, I won't read it - I might be exposed to ideas which contradict my world-view, and this makes me more scientific than you! La la la not listening!" the material keeps getting removed.

I'm by no means an expert on this subject, and it wasn't me who added this material in the first place. If anyone puts forward *ANY* substantial criticism of the material then I will be the first one to argue for its removal. But having read the book in question and found it impressive, and having checked several of the references in the book itself, and found them to make sense, it will take more than "it must be bad because it uses a bad word" to convince me this material should be removed. Stealth Munchkin 20:51, 1 January 2006 (UTC)

It is disengenuous of Stealth Munchkin to claim that the only objection to inclusion of the microevolutionary model is the word ascorbate, when there is a long and rambling discussion of the subject, with a number of other points against, in the section directly above this one.Jellytussle 21:00, 1 January 2006 (UTC)

Those points consist mostly of ad hominem attacks, arguments against the use of vitamin K (which is nothing to do with the validity of the model itself), and an argument about aneuploidy, which is not referred to in the article and which I am not competent to judge. Show me a single argument *against what is in there* Stealth Munchkin 21:19, 1 January 2006 (UTC)

What we do have, Munchkin, is Wikipedia:No original research.

And this is not original research, as it is from an outside source, not from the editor who put this material in.

I am not so concerned about that as the fact that according to NPOV policy, emphasis should be given on viewpoints which currently hold most significance or the majority...ie. represent alternate viewpoints, but they should not dominate other viewpoints. The current section does this, and that is why I would support a paragraph or so mentioning this new hypothesis, but especially not with redundant info that supports clonal evolution as though it supports microevolutionary model against clonal evolution, as it currentlys seems to do. I object to the material on the grounds that - most of it is not a new theory, and should go under clonal evolution, and that the rest of it (concerning "eureka! revolutionary!" and the entire thing of using antioxidants as the dominant way to prevent cancer) should be re-worded and npov'ised. -- Elle vécut heureusement _{toujours dorénavant} (Be eudaimonic!) 21:01, 1 January 2006 (UTC)

Fine, so reword it. Cut the material down. What I am arguing against is the *removal* of the entire section. The "entire thing of using antioxidants as the dominant way to prevent cancer" of which you speak consists of *one sentence* in this article - "The microevolutionary model predicts that antioxidant substances should prevent the development of cancer in the early stages." No-one is arguing that that section is to be left sacrosanct and inviolable. What I am arguing is that it is better to keep information than delete it, and given that no-one has yet proposed a reason for deletion based on the actual content in the disputed section, I would always err on the side of keeping the material. Stealth Munchkin 21:19, 1 January 2006 (UTC)

Again, if Munchkin would take the trouble to look in the section above this one, he/she will see that a number of reasons have been given why this section should be removed entirely from the Carcinogenesis page. It can become a stand alone article or a section of a page on unconventional medical theories. That is not the same as deleting it altogether.Jellytussle 21:26, 1 January 2006 (UTC)

Immune selection in neoplasia: towards a microevolutionary model of cancer development PMID: 10864195 seems to be a legitimate paper regarding a microevolutionary model for neoplasia. If someone who has a BJC subscription can look at it, perhaps we can assess the validity of this. This article appears to be unrelated to any orthomolecular claims. I fear there may be conflation of a legitimate scientific hypothesis and similarly worded advertisements for antioxidants. --DocJohnny 01:55, 2 January 2006 (UTC)

Which 'advertisements for antioxidants' are these? Are you implying that Hickey and Roberts, or perhaps some of those who have contributed to this and other articles, have any financial stake in the sale of antioxidants? If so, do you have any evidence whatsoever for this allegation? For someone who appears never to have read the book in question, or any other works by the authors, you seem very confident that the ideas contained therein cannot possibly be of any significance.Stealth Munchkin 17:54, 2 January 2006 (UTC)

My confidence arises from the fact that this is a self-published book rather than a peer reviewed article in an actual scientific journal. I am implying nothing and allege nothing. What you infer is your own business. --DocJohnny 18:54, 2 January 2006 (UTC)

You referred to 'advertisements for antioxidants'. Which advertisements are these? It seems like almost every argument against the inclusion of this material is based on phrases like that which have no basis in the text, or indeed in reality. You seem to be making a hell of a lot of assumptions about something you have not actually read. I *have* read the book and say that whether right or wrong it is well-researched and well-referenced, by well-qualified, respected scientists whose credentials and experience are on public record. You on the other hand have not read the book and say it is an 'advertisement for antioxidants'. Try actually reading the material *before* attacking it - it may help. Stealth Munchkin 20:31, 2 January 2006 (UTC)

My assumptions are based on the article and section inserted here. It is my opinion that a self-published book does not meet the standards for inclusion into a scientific article. As I have not read the book, I cannot accurately comment on its research or its references, but the articles here do not inspire faith, and well-qualified, respected scientists publish in journals, not self-publishing sites on the internet. As for the phrase 'advertisements for antioxidants', that is a POV phrase that reflects my POV just as it is my POV that this is a orthomolecular version of Intelligent Design. As such, I obviously did not include it in the article. Also, I am not attacking your book, I just don't think self-published books are really notable, especially in scientific articles. If it is as good as you say, you should have no problem getting it published in a real journal. Try the BJC. --DocJohnny 21:17, 2 January 2006 (UTC)

You appear to be under the impression that I am either Steve Hickey or Hilary Roberts. I am neither.Stealth Munchkin 22:53, 2 January 2006 (UTC)

My mistake. --DocJohnny 23:05, 2 January 2006 (UTC)

I saw that abstract when I did a search last week. Although it uses the term microevolution, it appeared to me that the word was being used to describe something different from that which is being discussed here. I will pull the article next week, and check to see where it has been cited.Jellytussle 03:30, 2 January 2006 (UTC)

Yes, that is the kind of microevolution I am familiar with, not the one purported by the two authors. -- Elle vécut heureusement _{toujours dorénavant} (Be eudaimonic!) 04:43, 2 January 2006 (UTC)

Again, I propose that a self-published book does not qualify as a credible source for a scientific article. --DocJohnny 18:47, 2 January 2006 (UTC)

Have you read the aknowledgements and preface in the book? If so you will know that the book was reviewed before publication and has a wikistyle continuing peer review process. Get real. TONS.

I remain real. In my reality self-published books are not equivalent to peer reviewed scientific journals. --DocJohnny 19:07, 2 January 2006 (UTC)

Once again for your benefit - the book is peer reviewed. it also contains over a thousand references to peer reviewed articles. Also the wikientry is slowly building up a long list of solid references. Your prejudice is showing. If you have an objection -please base it on scientific fact. TONS

Why take this personally? Lack of a scientific peer review is a legitimate complaint. If this is good science, get it published in a journal. No one is likely to accept peer review in a self-published work where we have no idea who the peers are. Also referencing peer reviewed articles does not mean the conclusions are correct, or even that the citations are correct. Only getting published in a recognized peer reviewed journal will lend legitimacy.--DocJohnny 19:31, 2 January 2006 (UTC)

I have read the review paper mentioned by DocJohnny previously: Immune Section in Neoplasia: Towards a Microevolutionary Model of Cancer Development Petit SJ, Seymour K et al BJC (2000) 82(12), 1900-1906 This is very much mainstream and has nothing whatsoever to do with the "microevolution" which is being touted on this page. In fact one could argue that the ideas being pushed here constitute misappropriation and misrepresentation of a title and an idea which has been previously published in a peer reviewed journal. That would not be permitted in normal academic circles.Jellytussle 19:43, 3 January 2006 (UTC)

Isn't that how all pseudoscience starts? By misusing scientific terminology to sound more serious? JFW | T@lk 19:54, 3 January 2006 (UTC)

Peer Review

Peer review is a process that ensures quality in scientific articles. For peer review to have meaning we have to be able to trust the "peers" which is generally selected by the journal. In other words, we also have to trust the journal. In a self-published work, this has no meaning. Who selects the "peers" for a peer review? If the author does, that violates the very premise of an unbiased peer review. And clearly the publisher printing agent cannot do so in this case. This is a publisher printing agent who also publishes prints a book that teaches you "God's foods" that cure AIDS, cancer, etc. and books that purport Flaxseed oil cure cancer by hardening on the cell wall of cancer cells and causing cancer starvation. A self-published book just has no credibility.--DocJohnny 21:30, 2 January 2006 (UTC)

Encore! Some brilliant sleuthing there! JFW | T@lk 18:21, 3 January 2006 (UTC)

Yes brilliant confusion and fun to read! Lulu is not the publisher but a printing agent. This level of argument might be considered to lack merit. TONS

Corrected! Nevertheless, the message is unchanged. A self-published book has no credibility. --DocJohnny 19:03, 3 January 2006 (UTC)

Vitamins & Cancer

The commentary below is quite negative & blunt, no offence is intended and I do genuinely look forward to further research & development in the understanding of nutrition :-)

• Whilst the "anti-oxidant" vitamins may remove free radicals that are known to be able to inflict tissue damage, and certainly vitamin deficiencies are separately associated with a range of diseases, the arguments generally given of: "vitamins having a role to play in cancer formation and thus vitamin supplementation has a role for prevention" is poorly thought out logical jumps. The problem is that whilst a deficiency of a nutritional substance may cause illness, so might its excess. With regard to the vitamin issue, it has been suggested that the body's own mechanisms to dealing with abnormal cells may require the use of free-radicals to effect the elimination of these pre-cancerous cells. e.g. see "Both suboptimal and elevated vitamin intake increase intestinal neoplasia and alter crypt fission in the ApcMin/+ mouse" 1 and this comes from the journal Carcinogenesis ! Also “The Ambiguity Of Molecular Cancer Chemopreventive Strategies” 2
  • The issues are contentious and under continuing research, but that should not grant them equal acceptance to the current understanding of a subject.
• This is not the place to discuss the issue of usage of multivitamin dosages in general (e.g. Vitamin C and the common cold), but the general accepted scientific (i.e. peer-reviewed journals, double-blind trials etc) and thus medical opinion, is that most of this is plain alternative pseudo-science. Such issues are interesting for their sociological commentary and thus worthy of inclusion in WP on that basis, but not for forming substantive equal-prominence within scientific factual articles.
• As JFW points out above, a single source is rarely sufficient for general acceptance of a scientific theory, and "evidence" published in a book rather than peer-reviewed journal is likely never so. The assumption of unimportance is usually correct (think of how many fad-books on dieting there have been)
• Yes the title of the book referred to, "Cancer: Nutrition and Survival", is automatically going to be considered by doctors at best suspicious, and any ideas arising from it as likely to be alternative medicine.
• It is of course important for Doctors to remain generally abreast of developments in medical research and react positively to these for the benefit of their patients. As important, is to react negatively to the large numbers of "latest ideas" one hears about from single individuals, self-promoting books/websites/articles in the media for the prevention of harm to their patients.
  • Doctors tend therefore to be seen as quite conservative or cynical in their rejection of the latest fashionable theories, but have tended to “have seen it all before”.
• So any article making reference to how free-radicals form a better understanding of cancer and its prevention is going to be seen with extreme healthy suspicion. Whether the idea develops into something more substantive (a start would be some experimental data published for peer-review and then repeated by other researchers) remains to be seen, but this does not make the idea one that is generally accepted, indeed must currently be seen as a minority opinion. WP is not about publishing the results of all underdeveloped propositions, and certainly not in the POV manner that this section has. I'ld agree with JFW's "unscientific" feeling that the topic sounds interesting, but that does not necessarily make it so.
• Vote to Move - This section therefore should be reduced to a link to the full topic, which for the time being must be considered as alternative-medicine. davidruben 06:10, 3 January 2006 (UTC)

Well said, Dr Ruben. A link to an alternative hypotheses page would be reasonable, but there is no reason for a direct link to microevolution from carcinogenesis. It is one of very many alternative hypotheses relating to cancer. Vigorous promotion on wikipedia by some enthusiasts does not qualify microevolution for any form of direct recognition from a subject which has a very extensive and rigorous scientific base.Jellytussle 06:27, 3 January 2006 (UTC)

I've just cut the whole section out, and replaced it with a mention. I've linked the article on the microevolutionary model of carcinogenesis, in which these views can be dealt with in an NPOV manner, apart from the main article; they deserve a mention here, but half the article is far too much for a minority theory. There you go; there's now bags of room in the linked article to expand on this theory. -- Karada 23:39, 3 January 2006 (UTC)

Can we please lose the paragraph to the microevolution cancer theory. It is incorrect to say that it has anything to do with the orthodox biological idea called microevolution.Jellytussle 01:06, 11 January 2006 (UTC)

Science not Partiality

Cancer research has a poor record of success and needs new ideas to make progress. No evidence has been presented here indicating that cancer is any different from the rest of biology. Cancer obviously operates on an evolutionary basis. It would be unique if it did not. But the carcinogenesis page only contains a mention of "clonal evolution" and that is an empty link. THINK!

The microevolutionary model that you are trying to smear with associations of pseudoscience has more scientific support than the subsidiary mechanisms presented here as carcinogenesis. The totality of evidence for the secondary mechanisms for carcinogenesis support the microevolutionary interpretation! YOU JUST DON'T GET IT.

This comments page displays a partiality that prevents objective consideration of the issue. User:TONS.

You mean objective consideration to your original research? JFW | T@lk 15:25, 12 January 2006 (UTC)

"Cancer research has a poor record of success and needs new ideas to make progress."

Complete nonsense. Displays a profound ignorance of modern cancer biology, translational research, and clinical trials. Cancer research is fizzing with ideas. Real progress is being made all the time. No one denies that there is a lot of room for improvement.

"No evidence has been presented here indicating that cancer is any different from the rest of biology."

So? It is part of cell biology. Clonal selection is generally recognised. but that doesn't mean it has feathers and goes,"cluck!"

"Cancer obviously operates on an evolutionary basis. It would be unique if it did not."

I don't think anyone is disputing that Clonal Selection occurs. However, that is quite different from the "microevolutionary model" that you have been promoting, which is a confused jumble of badly connected assumptions.

I do not understand how uniqueness has anything to do with this. Unique compared to what? My big toenail?

"The microevolutionary model that you are trying to smear with associations of pseudoscience has more scientific support than the subsidiary mechanisms presented here as carcinogenesis."

Really? That strains credulity slightly. It also flies rather in the face of the obvious, as evidenced by the large amount of research funding, scientists, scientific literature, and clinical practice based around the conventional theories of carcinogenesis which are presented here, and in most textbooks of cancer biology and oncology.

Regards Jellytussle 01:56, 12 January 2006 (UTC)

I think TONS (talk · contribs) has not yet advanced a single shred of evidence that we should be taking the microevolutionary theory with anything more than a grain of salt. JFW | T@lk

Why is "induction" not mentioned in this article?

The disambiguation page Induction has one meaning "Carcinogenesis" (with link to this article), but the term "Induction" is not found in this article. Can this please be added? Badagnani (talk) 03:14, 16 December 2009 (UTC)

have removed from disambig page as no explanation found. Lee∴V (talk • contribs) 01:41, 23 March 2010 (UTC)

Merger proposal

Propose to merge oncogenesis with this page.

Reasons:

• they are either 100% synonyms or no clean distinct definitions can be found
• both need some work
  • the definition given in carcinogenesis is too narrow
  • more focus on systemic aspects like tumor formation, metabolism, angiogenesis, endocrine and imune system mechanisms, metastasis
  • explain oncogenic paradox, Peto's paradox
  • more comprehensive overview of evolutionary, alternative, complementary theories

Having 2 articles with nearly identical content is a waste effort and difficult to keep up to date.

Please whoever feels like doing it do it, I am not experienced with merges and do not have admin rights. Richiez (talk) 10:55, 18 September 2010 (UTC)

Support Admin rights are not needed to merge articles. First we should decide on which name we should go with. A google scholar search gives that "carcinogenesis" is used more frequently thus this seems like the reasonable choice. Also it seems like the more common lay term. If you wish to begin I can keep an eye on your progress.Doc James (talk · contribs · email) 18:14, 18 September 2010 (UTC)

Support merge. "Carcinogenesis" is the more widely used term. Axl ¤ [Talk] 08:58, 21 September 2010 (UTC)

That sounds reasonable. It may be time for a more systematic review of the articles in this area, to see where we have duplications, contradictions, or gaps. We should probably look at (for example) articles like malignant transformation as well, to see if they should be better tied in or merged as well. TenOfAllTrades(talk) 12:20, 21 September 2010 (UTC)

Have begun the merge. If others wish to join in. Doc James (talk · contribs · email) 20:23, 9 October 2010 (UTC)

What a bizarre article

I don't think there is any scientist who doesn't believe that chemical and physical mutagens and carcinogens are some of the prime driving forces of carcinogenesis (they cause mutations that can give rise to cancer), but there is so little mention of them and how they produce mutation in an article supposedly about the process of carcinogenesis. And what's mentioned, radiation and chemical mutagens, are placed under viral subsection? The shortest possible mention of chemical mutagens/carcinogens and radiation, instead we have a long passage on atavism. Then the only place where reactive oxygen species being mentioned as a cause of carcinogenesis is in the non-mainstream theories section. I don't think there is any scientist who doesn't believe that reactive oxygen species can be a cause of cancer. Are there any scientist contributing to this article? Hzh (talk) 13:23, 16 October 2011 (UTC)

Have moved section on cause up. --Doc James (talk · contribs · email) 13:58, 16 October 2011 (UTC)

Not sure if that helps, non-mainstream ideas should not be near the top (should be at the bottom). One way of describing carcinogenesis would be initiation, promotion and tumor progression (there are other ways of describing it), so a multi-stage description should be in the mechanism section in the right order. This might be multiple mutations (although some cancers appears to involve only one single mutation event), and there should be a section on carcinogen/mutation/mutagenesis for the initiation part. A bit more on non-mutagenic carcinogens is necessary I think. The organization of various sections needs to be improved. I'm not sure for example, why there are 2 clonal evolution subsections (the first one should be deleted or merge into the later one). I also would not use the word "natural selection" because it is a different idea. Hzh (talk) 18:44, 17 October 2011 (UTC)

I'm surprised to see no mention on this page at all of the multistage model proposed by Armitage & Doll (1954). I had come to this page to learn more about the model's relevance to the current interpretation of carcinogenesis, and am none the wiser. I would like to make these edits myself but know rather little about the details of either the reception of the Armitage-Doll model or how it relates to modern hypotheses on carcinogenesis.Jimjamjak (talk) 14:28, 27 October 2011 (UTC)

It's just a very unsatisfactory article. The multi-stage model must be mentioned, and there are quite a few things needed to be done. The problem with this is that it requires a massive rewrite, and I don't have the time to do it at the moment. Someone with the time and inclination can perhaps make a start and I can contribute later if I have the time. Hzh (talk) 22:29, 2 December 2011 (UTC)

Inflammation and cancer

inflammation seems to play an important role in the process of cancer development. See for example the following article:

"Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development." http://www.ncbi.nlm.nih.gov/pubmed/12490959

Or this article: "A new study shows how inflammation can help cause cancer. Chronic inflammation due to infection or to conditions such as chronic inflammatory bowel disease is associated with up to 25 percent of all cancers." http://www.sciencedaily.com/releases/2011/04/110419091159.htm and http://dx.doi.org/10.1073/pnas.1101795108 — Preceding unsigned comment added by 79.199.39.228 (talk) 17:29, 6 April 2012 (UTC)

you can google to find more papers with reliable sources: http://scholar.google.de/scholar?q=Inflammation+and+cancer

i think these informations should be included into the article. i have not the knowledge in this area to do it. can anybody help?

79.199.39.228 (talk) 17:36, 6 April 2012 (UTC)

Blebbishield emergency program, etc

I'm moving the content of this edit to the talk page, per WP:UNDUE (I think), as a search term, "blebbishield" currently gets just 8 hits on Google Scholar.

Cellular transformation is essentially sphere formation of cancer cells. Recent findings demonstrates that cancer stem cells can form spheres (transformation) after undergoing morphological and biochemical apoptosis by evoking blebbishield emergency program.

109.158.8.201 (talk) 22:04, 29 December 2014 (UTC)

Assessment comment

The comment(s) below were originally left at Talk:Carcinogenesis/Comments, and are posted here for posterity. Following several discussions in past years, these subpages are now deprecated. The comments may be irrelevant or outdated; if so, please feel free to remove this section.

The article is lacking inline references. - tameeria 23:08, 29 April 2007 (UTC)

Last edited at 23:08, 29 April 2007 (UTC). Substituted at 10:53, 29 April 2016 (UTC)

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