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Applying evolutionary principles to cancer treatment

ResearchBlogging.orgEDITOR’S NOTE: Unfortunately, this weekend, I was forced to get my slides together for the upcoming SBM Conference, plus editing a manuscript for resubmission, plus working on a manuscript that I should have submitted six months ago, plus reading over some grants, plus…well, you get the idea. What this means is that, alas, I didn’t have any time to prepare one of the new, long posts that you’ve come to love (or hate). Fortunately, there are a lot of other things I’ve written out there that can be rapidly adapted to SBM. For instance, what I am about to present now. Since I wrote this, I’ve thought of a couple of things that I should have said the first time (and was kicking myself for not having done so); so publishing an updated version here allows me to rectify those omissions.

A couple of weeks ago, there was a lot of hype about a study that hadn’t been released yet. Indeed, there was a story in Wired entitled To Survive Cancer, Live With It and an editorial by the study’s lead author in Nature entitled A change in strategy in the war on cancer. Not bad for a study that hadn’t been released yet. Intrepid medical and science blogger that I am, I waited until the actual study was published a week ago the June 1 episode of Cancer Research. It’s a clever study, but the hype over it was a bit overblown. For example:

For all the weapons deployed in the war on cancer, from chemicals to radiation to nanotechnology, the underlying strategy has remained the same: Detect and destroy, with no compromise given to the killer. But Robert Gatenby wants to strike a peace.

A mathematical oncologist at the Moffitt Cancer Center, Gatenby is part of a new generation of researchers who conceive of cancer as a dynamic, evolutionary system. According to his models, trying to wipe cancer out altogether actually makes it stronger by helping drug-resistant cells flourish. Rather than fighting cancer by trying to eradicate its every last cell, he suggests doctors might fare better by intentionally keeping tumors in a long-term stalemate.

Maybe I’m being a bit picky, but what annoys me about the news reports on this study is that the concept of turning cancer into a manageable chronic disease like diabetes or hypertension is not by any means a new idea. Remember, one of my major research interests is the inhibition of tumor angiogenesis. Consequently, I know that the late, great Judah Folkman first proposed the concept of using antiangiogenic therapy to turn cancer into a chronic disease at least as early as the mid-1990′s. The only difference is the strategy that he proposed. The idea had also been floating around for quite a while before that, although I honestly do not know who first came up with it.

But let’s see what Dr. Gatenby proposes. What makes it interesting is that his study actually looks at how scientists have applied evolutionary principles to cancer until recently, argues that we’ve been doing it wrong. He then proposes a way to use the evolutionary dynamics of applied ecology. He may well be on to something. First, here’s the problem:

The German Nobel laureate Paul Ehrlich introduced the concept of ‘magic bullets’ more than 100 years ago: compounds that could be engineered to selectively target and kill tumour cells or disease-causing organisms without affecting the normal cells in the body. The success of antibiotics 50 years later seemed to be a strong validation of Ehrlich’s idea. Indeed, so influential and enduring was medicine’s triumph over bacteria that the ‘war on cancer’ continues to be driven by the implicit assumption that magic bullets will one day be found for the disease.

Yet lessons learned in dealing with exotic species, combined with recent mathematical models of the evolutionary dynamics of tumours, indicate that eradicating most disseminated cancers may be impossible. And, more importantly, trying to do so could make the problem worse.

Traditionally, cytotoxic chemotherapy has been given in either as fixed doses close to the maximum tolerated dose or, as has been common more recently, a regimen known as “dose dense.” Basically, the fixed dose schedules involve giving as much chemotherapy as the patient can tolerate up to what is known as the “maximum tolerated” dose and giving it over as short a period of time as possible, while “dose-dense” therapies try to target chemotherapy doses to the time of maximal tumor growth, when tumors are maximally sensitive to chemotherapy. This strategy is based on what is called the Norton-Simon model. One key assumption behind such therapies is that chemotherapy fails because of the evolution of resistant cells after chemotherapy has begun. The idea behind this strategy is to hit the tumor cells as hard as possible as fast as possible to kill as many cells as possible and minimize the opportunity to develop resistance. Dose-dense chemotherapy has definitely resulted in improvements in survival in multiple tumors but rarely results in cure, at least in the common “solid” malignancies that kill so many, such as breast, prostate, lung, and colon cancer. However, that improvement sometimes comes at a price: Increased toxicity and side effects.

Based on Judah Folkman’s work, around the turn of the century (the 21st century, not the 20th century) Robert Kerbel proposed a new regimen known as metronomic chemotherapy. Metronomic therapy involves giving chemotherapy either continuously or at frequent dosing but at a much lower dose, the idea being that, because blood vessels are lined by genetically stable endothelial cells, they do not evolve resistance, and chemotherapy can be antiangiogenic. The idea was to deliver the same total dose of chemotherapy but without all the toxicity, meanwhile keeping the tumor in check or shrinking it by the effect the chemotherapy has on the tumor blood vessels. The drawback is that long periods of therapy may be required and the cumulative doses may end up being actually higher than more standard therapies. On the other hand, this latter aspect may not be a drawback because metronomic chemotherapy may allow a greater cumulative dose, with a concurrent greater cumulative effect. Metronomic chemotherapy is a promising concept, but thus far clinical trials in humans have been fairly disappointing.

One aspect that is shared among both of these therapy modalities is that they generally both involve fixed schedules and fixed doses. What Dr. Gatenby proposes to get around this is to apply what he calls “adaptive therapy.” This therapy is based on population ecology and the observation that the development of resistance does not come free. Indeed, resistant cells need to expend energy in order to do what cells do to overcome chemotherapy; for exmple, to repair DNA faster, pump the chemotherapy out of the cell, bypass intracellular signaling pathways blocked by new targeted therapies, or crank out enough peptides that induce the ingrowth of new blood vessels in order to overcome therapies that block these factors. In other words resistant cells tend to have a lower fitness under normal conditions. It is only the selective pressure of chemotherapy that allows resistant cells to proliferate faster than normal cells, and, indeed, resistant cells tend to lose their resistance when the selective pressure is removed.

Given this concept, Gatenby likens adaptive therapy to controling invasive species:

Gatenby: How people treat invasive species can provide an analogy for thinking about cancer therapy. In treating a field for a pest, for example, you might treat three-quarters of it with a pesticide, and leave the other quarter untreated. Pesticide-sensitive pests remain there, and they spread out into the field after treatment, preventing pesticide resistance from becoming dominant.

Using pesticides on an entire field is like what we’re doing with cancer now. And we all agree that we’d rather get rid of the pests altogether, but if you can’t do it, if every time you have an infestation you treat it and get resistance, then you try a different strategy. The alternative is to try to reduce the pest population so that it doesn’t damage your crop, and accept the fact that they’re going to be there. That’s what I’m talking about with cancer.

Wired.com: What type of treatment would that involve?

Gatenby: Instead of fixing the dose of the drugs, you fix the size of the tumor. Your whole goal is to keep the tumor stable. You continuously alter the drug, the dose, the timing of the dose, with that goal in mind.

And:

Our models show that in the absence of therapy, cancer cells that haven’t evolved resistance will proliferate at the expense of the less-fit resistant ones. And, when a large number of the sensitive cells are killed, for instance by aggressive therapies, the resistant types are able to proliferate unconstrained. This means that high doses of chemotherapy might actually increase the likelihood of a tumour becoming unresponsive to further therapy.

So, just as the judicious use of pesticides can be used to successfully control invasive species, a therapeutic strategy explicitly designed to maintain a stable, tolerable tumour volume could increase a patient’s survival by allowing sensitive cells to suppress the growth of resistant ones.

It’s a fascinating concept. The idea is to keep from killing off too many of the sensitive cancer cells, so that they can grow to a certain point and keep the resistant cells in check. But can it work?

The Cancer Research paper published a week ago presents evidence that, at least in mouse models, it might be able to. I will admit that a lot of the mathematics in the paper are beyond me. There was a time when I was in college and taking all sorts of calculus and differential equations when these equations wouldn’t make my brain hurt to look at them, but if you don’t use it you lose it, and lost it I have (mostly). Suffice it to say that the model takes into account estimates of variability of fitness in tumor cells making up the population, dosing, differential uptake with tumor size, and other critical parameters. The concept of adaptive therapy requires that chemotherapy doses be adjusted to maintain constant tumor volume, increasing dosage if the tumor grows and decreasing it if the tumor shrinks. First, the mathematical model:

Fig3

The graphs above represent modeling of dose dense/maximum tolerated dose (MTD) therapy, adaptive therapy, adaptive therapy (ADAP), and three varieties of metrnomic therapy, continuous infusion, high frequency, and low frequency. Four combinations of mixed cell populations were tested, including:

  1. FR with high free-field fitness and high sensitivity to therapy
  2. R with lower fitness and low sensitivity to therapy
  3. S with low fitness and high sensitivity
  4. ER with high intrinsic sensitivity and fitness but in an environment that restricts proliferation and response.

Combinations that were modeled included: (a) ”FS and R,” (b) ”S and FR,” (c) ”FS and R and ER,” and (d) ”FS and ER.” Strikingly, by day 1,500 of tumor growth (1,100 days after therapy was started), the tumor treated using the MTD strategy had grown to be the largest whereas those treated with metronomic therapy were smallest. When the simulations were run out to many thousands more days, until the tumor burden achieved the lethal threshold, all patients in the MTD and metronomic therapies eventually succumbed to their disease. In this model the tumors treated with adaptive therapy remained stable even after a period exceeding 10,000 days. In other words, tumors treated with MTD had the best initial response rate to therapy but tended to develop resistance rapidly, while tumors treated with metronomic chemotherapy remained stable and did not grow appreciably for much longer but nonetheless eventually developed resistance to the point where the tumor escaped therapy and killed the host. In contrast, tumors treated with adaptive therapy remained stable for a very long time.

Mathematical models are all well and good, but does adaptive chemotherapy work for real? To test that, Gatenby designed an adaptive therapy protocol for a mouse model of ovarian cancer. It was a tricky experiment to do, as his group had to measure the tumor burden every three days and then adjust the chemotherapy dose according to their behavior, decreasing the dose for each mouse if its tumor shrank and increasing the dose if it grew. All of this was done fore each and every mouse, meaning that there could be as many doses of chemotherapy as there were mice in the adaptive therapy group. Here’s the method:

The adaptive group received an initial dose of 50 mg/kg and thereafter the tumors were evaluated every 3 days and the dose was adjusted to maintain a stable tumor volume. The algorithm for dosing basically represented “a shot in the dark” because no prior experience was available to parameterize the models. Drug doses were established in increments of 10 mg/kg starting at the starting dose of 50 mg/kg. A treatment decision was made at the time of each measurement. If the tumor remained stable (defined as the no more than a 10% change from the prior volume using caliper measurements), no drug would be administered. If the tumor diminished in size or remained stable for two or more measurements, the next dose would be decreased by one 10 mg/kg decrement. If the tumor increased in size greater than 10%, the same dose of drug would be administered. If the tumor again increased in size, the dose would be increased to the next higher level.

As you can see, this is a pretty labor intensive regimen. No doubt Gatenby will be able to refine his method and develop a protocol that isn’t in essence a reasonable guess, but for now there isn’t a lot to guide scientists in developing such adaptive protocols.

Here’s the result:

08-3658 4894..4903

In the mice, the adaptive regimen using carboplatin clearly worked better than the standard carboplatin regimen, suggesting that adaptive therapy can work. As Gatenby puts it:

Our analysis shows that, in the absence of therapy, the fitter, chemosensitive cells actually suppress the growth of the less fit but resistant population. Therapies designed to kill maximum numbers of cancer cells produce an environment in which the resistant cells both survive and are unopposed by the fitter, chemosensitive populations. This permits rapid regrowth of a therapy-resistant cancer. Alternatively, if therapy is limited to allow a significant number of chemosensitive cells to survive, they will, in turn, suppress the growth of the resistant population. We hypothesized that under these circumstances, adaptive therapy should be designed to maintain a normal cohort of surviving sensitive cells.

Another interesting aspect of this study is that it’s been known for some time that using metronomic chemotherapy allows a larger total dose of chemotherapy given over a longer period of time with lower toxicity. It works well in mice, but unfortunately is less stunningly effective in humans (much like antiangiogenic therapy, alas). The larger total dose of chemotherapy that can be delivered is one reason that has been postulated as an explanation for why metronomic chemotherapy can be more effective than dose dense chemotherapy. There’s no reason to think that adaptive chemotherapy wouldn’t behave similarly and allow for a larger total dose. But, in this model at least, it went beyond that. The adaptive chemotherapy group the dose required to maintain tumor stability decreased with time from 50 mg/kg to 10 mg/kg. In the experiment I showed, the individtual doses were 50, 40, 40, 30, 30, 20, 20, 10, 10, 10, 10, 10, 10, 10, 10, 10 mg/kg. This observation is consistent with a stabilization of the tumor cell population consistent with the evolutionary and ecological model used to test the study hypothesis.

The power of evolutionary principles is that they apply to more than just populations of organisms. They can equally apply to populations of cells within an organism, like cancer. In other words, evolution acts at both the organism level and the cellular leve. Tumors, given their genetic instability, enormous heterogeneity, and subpopulations of cells with different fitness and sensitivity to selective pressures are a perfect system to apply the principles of evolutionary ecology to. What’s fascinating about this study is that it appears that using evolutionary principles in a savvier way than we have in the past can work. In theory and in at least one animal model, it can produce more effective chemotherapeutic regimens. Indeed, one fascinating observation is that, the longer the tumors were treated with adaptive therapy, the less chemotherapy was required and the longer the intervals between doses that were needed to maintain a constant volume. Like the concept of antiangiogenic therapy proposed by Judah Folkman, however, applying evolution to cancer may require a rethinking of how we deal with cancer.

Unfortunately, I don’t see an obvious or immediate application of adaptive chemtherapy in humans. The reason is that it would be very cumbersome, labor-intensive, and expensive. Tumor measurements far more frequent than what we routinely do now would be required, as would frequent adjustments in chemotherapy dosing. As a strictly practical matter, it would be very hard to implement. Indeed, this model was very simplistic in that it tested adaptive chemotherapy using one drug. In reality, very few chemotherapy regimens in common use involve only one drug, and any truly adaptive therapy would have to adjust multiple drugs, with a concomitant exponential increase in complexity administrating it. Also, from a strictly clinical standpoint, tumors that are large or advanced would need to be shrunk because their size causes serious symptoms. How that would be integrated into an adaptive regimen remains to be seen.

Another potential problem is one that has been seen by scientists trying to use a similar approach to control HIV infection: compensatory mutations. In antibacterial therapy, the long term removal of antibiotics has not thus far resulted in the disappearance of resistant strains, and this is due to compensatory mutations that can restore the fitness of these strains. This phenomenon has only been described in viruses and bacteria, but it would not be surprising if they also occurred in cancer cells.

Even so, there is one potential use that I can envision for this sort of ecological approach to produce adaptive chemotherapy. This would be as a means of treating tumors that have well-validated serum tumor markers that correlate well with tumor burden in individual patients; for example, colorectal cancer (tumor marker: carcinoembryonic antigen, or CEA) or prostate cancer (tumor marker: prostate-specific antigen, or PSA). One can imagine an implantable pump that could measure the levels of these tumor markers and then, according to algorithms developed based on ecological and evolutionary principles, continuously adjust the dose of metronomic chemotherapy to keep a patient’s tumors in check.

Finally, as Gatenby himself points out, these sorts of approaches will not render the search for cures unnecessary. After all, consider other chronic diseases. Diabetes, for instance, can be managed quite well on a chronic basis, but what patient with type I diabetes wouldn’t want to be cured and thus able to throw away his insulin syringes? In the case of cancer, cures remain preferable, but, like the case of diabetes, sometimes settling for chronic management is the best we can do.

REFERENCE:

Gatenby, R., Silva, A., Gillies, R., & Frieden, B. (2009). Adaptive Therapy Cancer Research, 69 (11), 4894-4903 DOI: 10.1158/0008-5472.CAN-08-3658

Posted in: Basic Science, Cancer, Science and Medicine

Leave a Comment (66) ↓

66 thoughts on “Applying evolutionary principles to cancer treatment

  1. wales says:

    Very interesting and educational. Even somewhat objective. Perhaps Oprahfication hasn’t permanently addled your brain (yet).

  2. adwkiwi says:

    Very interesting, and it taps into some interesting things I’ve been hearing about how medicine can get seriously about evolution recently (Frank Ryan spoke at a recent Cafe Scientifique about just this).

    It brings to my mind adaptive psychophysical methods in perception research, which test a response and adjust the level being tested up or down depending on whether you’re correct or not. There are numerous very efficient (mostly Bayesian) algorithms for driving these step changes that are in common use in psychology – maybe they could be useful here?

    And re: getting this efficient enough for human use – I’m in a similar position in my own research, namely I have a handy task but I need to spend time getting a handle on how to optimise using it. If there’s one thing I’ve learned, there’s no substitute for just trying a bunch of stuff out :)

  3. Wallace Sampson says:

    Excellent explanation, David. The immediate and personal significance might help some of the some trolls and snipers understand the honest and logical investments that drive medical science. At least one can hope.

    I have a personal experience with the concept. The thought may have occurred to many others spontaneously, or the thought might have been induced from basic biological principles. My predecessor at my last position believed in the concept and gave suboptimal doses routinely in non-curable cases hoping for the same effect. Patients liked it. But it did not go over well with staff and other oncologists. There may have been a few curable patients who did not receive curative doses. That was debatable, yet I was the beneficiary. The previous doc may yet have the last word.

    But what evidence was there for using max tolerable doses in non-curable cancers? There was some evidence, but not much. We knew it, and the patient cost in toxicity was considerable – and still is. My preference – not to treat resistant cancers with chemo.

    There are equally fertile concepts to pursue, such as overcoming multiple drug resistance including resistance to cell membrane transport, ideal timing according to cell cycling drug susceptibility, and so forth. So many theories, so few options.

  4. pec says:

    “The success of antibiotics 50 years later seemed to be a strong validation of Ehrlich’s idea. Indeed, so influential and enduring was medicine’s triumph over bacteria that the ‘war on cancer’ continues to be driven by the implicit assumption that magic bullets will one day be found for the disease.”

    What I and other holistic health wackos have been trying to explain for decades is that the bacterial infection model may be the wrong model for cancer. Cancer cells may often be a symptom rather than a cause of disease, and this may explain why a cure has not been found for most types of cancer. A bacteria infection is, generally, a very different kind of disease — bacteria sometimes attack an otherwise healthy person, and killing the bacteria can solve the whole problem. (This is not always true, of course, because sometimes bacterial infections are the result of other diseases which have weakened the immune system.)

    There are similarities between bacterial infections and cancer, but there are also important differences. Cancer research has focused on the similarities, relentlessly seeking magic bullets and ignoring other possible models.

    The new ideas described in this post stick with the old view of cancer cells as attacking invaders, rather than a result of a systemic disorder.

  5. Harriet Hall says:

    “Cancer cells may often be a symptom rather than a cause of disease.” I thought cancer cells WERE the disease.

  6. David Gorski says:

    They are.

    pec is parroting various woos known as the German New Medicine, or its more recent variant Biologie Totale, as well as the sort of nonsense posited by Robert O. Young. There’s a whole subgenre of cancer quackery that postulates that cancer is not a “disease” but rather a manifestation of something else. In the case of the German New Medicine, it’s supposedly a manifestation of life traumas that show up as cancer and if you can identify and fix the life traumas you can cure cancer. In the case of Robert O. Young, he claims that cancer is a reaction of the body to cells “spoiled” by “too much acid.” He even goes so far to claim that the cancer is an attempt by the body to encapsulate these “spoiled acid liquid cells” and thereby protect itself from them. His answer? Cure cancer by “alkalinization.”

    In any case, this whole “cancer is a symptom not a disease” nonsense is pretty prevalent in cancer quackery.

  7. pec says:

    I was NOT talking about any of the quacks you listed! I am talking about a general belief in holistic medicine. You try to make it sound ridiculous by only mentioning the wackiest proponents. But MOST holistic health theorists would probably agree with me. And they are not all quacks, even though of course you would like to think so.

  8. pec says:

    [“Cancer cells may often be a symptom rather than a cause of disease.” I thought cancer cells WERE the disease.]

    Yes of course that’s what you believe, because you were taught the infectious disease model of cancer. That may be valid for certain types of cancer, but I think for many other types it is very wrong. Mainstream cancer research has pretty much been barking up the wrong tree for decades, and you have the results to prove it.

  9. David Gorski says:

    That may be valid for certain types of cancer, but I think for many other types it is very wrong.

    Really? Do tell.

    For instance, do tell us specifically which cancers are the primary disease and which ones are a “symptom.” Please also do tell us what scientific evidence leads you to your conclusions. I’ll wait. (I ‘ll have to wait, because I’m going to be working too much the rest of the day to check on the blog until sometime this evening.)

  10. pec says:

    [ do tell us specifically which cancers are the primary disease and which ones are a “symptom.” Please also do tell us what scientific evidence leads you to your conclusions.]

    This is what alternative medicine has always believed — that healthy immune systems routinely destroy or contain cancer cells, and cancer cells only cause disease when the immune system is for some reason weak or defective. This theory is backed up by the autopsy studies showing that cancer cells are often present when the patient died from old age, and was never diagnosed with cancer.

    There may be some types of cancer that are caused by genetic defects or exposure to environmental toxins, which the immune system could never have handled. That type might fit the infectious disease model, but many other types probably do not.

    Since the big research funding has always gone to the infectious disease model, I don’t know how much controlled experimental evidence there is for the alternative theories. The alternative theories seem to be worth checking out, I would say, considering the abysmal results for the mainstream theories.

  11. Scott says:

    Translation of pec’s last post:

    I have absolutely no actual grounds to believe any of this. It’s been pulled out of the ether and various bodily orifices by people engaging in wild speculation. And scientific medicine isn’t perfect, therefore I demand that you give my lunacy equal standing.

  12. weing says:

    So, elderly men with prostate cancer, with weak immune systems to boot, die from an unrelated illness. Somehow their weak immune systems are able to keep the cancers in check. Yeah, right.

  13. pec says:

    It is accepted even in mainstream medicine that many cancers do not progress or cause disease. Did you ever wonder why?

  14. weing says:

    Of course. That’s why I gave you a common example that flies in the face of your immune system theory.

  15. pec says:

    “That’s why I gave you a common example that flies in the face of your immune system theory.”

    weing,

    I never claimed to have a complete theory that explains everything about cancer. You probably realize that, but enjoy being difficult. I said that the mainstream theories seem to be inadequate, and that it might be helpful if cancer researchers would consider other models.

    I did not say cancer is always caused by a weak immune system. I said that might happen sometimes, or sometimes the immune system may be in some way defective.

    I do not claim to be all-knowing and to possess the truth about all types of cancer. I am saying that the mainstream researchers have an unwarranted confidence in the correctness of their approach.

    The great successes of antibiotics led them to approach cancer as if it were an infectious disease. Many years have gone by with little progress, yet they never stop and think that maybe their approach is wrong.

  16. Prometheus says:

    I’m not sure where “pec” gets the idea that cancer research is based on the “infectious disease model” (whatever that might be) or that cancer researchers are “ignoring” the contribution of the immune system. My guess is that this is an imperfect (or possibly perfect) regurgitation of some web-site or pamphlet on “alternative cures for cancer”. It certainly doesn’t come from an understanding of what is currently being done in cancer research.

    The fact is that cancer research is looking at ways to use the immune system to treat cancer and is already using immune system modulation as a treatment for certain types of cancer (see: http://www.mayoclinic.com/health/monoclonal-antibody/CA00082).

    To “pec”, it may look like cancer is being treated like an infectious disease, but not to anybody with actual knowledge of biology or medicine.

    Infectious disease therapies are generally directed at interfering with cellular (or viral) metabolic or genetic features that are different from human cells. Antibiotics target things like bacterial ribosomal subunits or cell wall synthesis, which human cells lack. Even anti-viral drugs target – as specifically as they can – enzymes or processes that are unique to the virus.

    Cancer therapies, on the other hand, are (by their nature) directed at human cells. They have to target the subtle shifts in balance that differentiate the cancer from the non-cancerous cells. Even the cell surface markers are often identical, making this a delicate job.

    Of course, “pec” also missed the fact that some cancers are infectious diseases. Oncoviruses – ever heard of them, “pec”?

    “Pec” also seems to have a rather blurry view of the recent progress in cancer research:

    Many years have gone by with little progress…

    Clearly, “pec” hasn’t been keeping up with the literature. Perhaps “pec” is concerned that nobody seem to be researching “the” cure for cancer – i.e. a single “theory-of-everything” blockbuster that will answer all questions about cancer and lead to a single monolithic “cure for all cancers”.

    Sorry, “pec” – that doesn’t exist. “Cancer” is not a single disease, doesn’t have single cause and won’t have a single “cure”. What cancer researchers have been doing is steadily cranking out more directed therapies and refining the use of existing therapies. Not as dramatic as an “herb” that will prevent prostate cancer (except when it doesn’t) or “boosting” the immune system (whatever that might be), but much more effective in the long run.

    “Pec” claims:

    I am saying that the mainstream researchers have an unwarranted confidence in the correctness of their approach.

    This comes across as simultaneously arrogant and ignorant, since “pec” has already demonstrated a serious lack of knowledge about the “approach” that “mainstream researchers” are taking to cancer. If “pec” doesn’t know what they are doing, how can she know that it is wrong?

    Prometheus

  17. pec says:

    [I’m not sure where “pec” gets the idea that cancer research is based on the “infectious disease model” (whatever that might be)]

    Did you read any of Gorski’s post?

    [The success of antibiotics 50 years later seemed to be a strong validation of Ehrlich’s idea. Indeed, so influential and enduring was medicine’s triumph over bacteria that the ‘war on cancer’ continues to be driven by the implicit assumption that magic bullets will one day be found for the disease.]

    [“Cancer” is not a single disease, doesn’t have single cause and won’t have a single “cure”.]

    I never said or thought or implied or hinted that it was.

    [If “pec” doesn’t know what they are doing, how can she know that it is wrong?]

    I don’t claim to know every detail about all cancer research. I doubt you or anyone does. But Gorski’s post was an explanation of a supposedly new attempt at finding a magic bullet. In other words, it continues the infectious disease model.

    I ‘m sure some researchers somewhere are looking at it in different ways. But I think we all know that the accepted mainstream treatments for cancer include surgery, radiation and chemotherapy.

    All are attempts to remove or destroy cancer cells, and none look for any cause other than the tumors, which I have been saying might sometimes be a symptom rather than a cause.

    You ignored most of what I said, and most of the original post. You skimmed a little and came up with your canned response to anyone who criticizes mainstream cancer research.

  18. David Gorski says:

    But Gorski’s post was an explanation of a supposedly new attempt at finding a magic bullet. In other words, it continues the infectious disease model.

    No it wasn’t and no it doesn’t. That you took that message home from my post demonstrates your profound lack of understanding of cancer and cancer research.

    This research was about applying a population-level ecology model to cancer, specifically modeled upon how farmers and biologists try to control invasive species when they can’t wipe them out. It’s not the first time this sort of thinking has been applied to cancer research, by the way. Perhaps I’ll repost something I wrote three years ago about another fascinating study that uses similar modeling and applies it to cancer progression.

    pec also reveals her ignorance when she says that cancer research neglects the contribution of the immune system to cancer development. Indeed, the study of the immune system and the development of immunotherapies have been one of the major strains in cancer research for decades now. pec may also be interested in knowing that chronic inflammation (which is mediated by the immune system) is a predisposing factor in many cancers and that, in fact, the process of inflammation can often lead to cancer. For example, Barrett’s esophagus results from chronic inflammation of the lower esophagus by acid from gastroesophageal reflux. It also greatly predisposes a person in whom it is found to the development of esophageal cancer.

  19. David Gorski says:

    [ do tell us specifically which cancers are the primary disease and which ones are a “symptom.” Please also do tell us what scientific evidence leads you to your conclusions.]

    This is what alternative medicine has always believed — that healthy immune systems routinely destroy or contain cancer cells, and cancer cells only cause disease when the immune system is for some reason weak or defective. This theory is backed up by the autopsy studies showing that cancer cells are often present when the patient died from old age, and was never diagnosed with cancer.

    There may be some types of cancer that are caused by genetic defects or exposure to environmental toxins, which the immune system could never have handled. That type might fit the infectious disease model, but many other types probably do not.

    In other words, pec can’t provide a single example to back up her assertion that many cancers are not the primary disease but rather the manifestation of some other disease process.

  20. pec says:

    “pec can’t provide a single example to back up her assertion that many cancers are not the primary disease but rather the manifestation of some other disease process.”

    “chronic inflammation (which is mediated by the immune system) is a predisposing factor in many cancers and that, in fact, the process of inflammation can often lead to cancer. ”

    Ok, you provided it for me: chronic inflammation, which is also a factor in heart disease. So it may be that the typical American lifestyle, which can result in chronic inflammation and metabolic syndrome, can also be the culprit in some types of cancer.

    A good example of what I have been trying to explain — thanks. And calling me ignorant might convince some of your readers that I am wrong, but real skeptics will see you’re just resorting to name-calling, again.

  21. weing says:

    pec,

    There is no shame in being ignorant of something that is not in your field of study. The holistic nonsense you mention is just that. Even your use of the word ‘symptom’ is nonsensical to a physician. To a physician a symptom is what the patient reports. It is a subjective finding. A sign is what the doctor verifies by his exam, tests, etc. It is an objective finding. A cancer cell is an objective finding. It is a sign, not a symptom. I know it may sound paternalistic, but that’s how it is.

    The claims you make for the holistic, if there is such a thing, as opposed to the mainstream approach sound like a straw man. Not being an oncologist, even I know that there are many models to cancer, not just one.

  22. David Gorski says:

    Ok, you provided it for me: chronic inflammation, which is also a factor in heart disease. So it may be that the typical American lifestyle, which can result in chronic inflammation and metabolic syndrome, can also be the culprit in some types of cancer.

    A good example of what I have been trying to explain — thanks. And calling me ignorant might convince some of your readers that I am wrong, but real skeptics will see you’re just resorting to name-calling, again.

    Nice try, pec, but my example most definitely does not show that cancer is not a disease, but rather a manifestation of another process. What my example shows is that chronic inflammation can lead to the disease of cancer.

    Try again.

  23. Zetetic says:

    Pec: There is continual reference to “strengthening the immune system” by the holistic crowd. Do they actually measure the immune system in some way (antibody titers?) to determine if it’s “weak”? How can they determine if their treatments actually do strengthen the immune system?

  24. Scott says:

    Not to mention the fact that strengthening the immune system is often a BAD thing. Autoimmune conditions, anyone?

    Particularly delicious since chronic inflammation is sometimes (maybe always, I’m not an MD) autoimmune. So if anything, the example pec’s happily latched on to demonstrates that strengthening the immune system could potentially CAUSE cancer! (Again, not an MD, but it certainly seems completely logical to me. I expect Dr. Gorski will correct me if I’m too far off base.)

  25. Zetetic says:

    I read a while back that the potential mechanism for the most severe symptoms leading to death during the great 1918-1919 “Spanish Flu” pandemic was an out of control immune response involving cytokines. Do we really want a “strong” immune system?!

  26. pec says:

    “What my example shows is that chronic inflammation can lead to the disease of cancer.”

    Yes, and you focus on killing the cancer cells, rather than looking at the underlying cause, the chronic inflammation. That has been exactly my point. Chronic inflammation shows that something is wrong with the system in general. You may succeed in killing some cancer cells and shrinking some tumors, but you would have done nothing to correct the actual disorder.

    And radiation and chemotherapy not only do nothing to correct the general disorder, their toxicity is likely to make things worse.

  27. pec says:

    [I read a while back that the potential mechanism for the most severe symptoms leading to death during the great 1918-1919 “Spanish Flu” pandemic was an out of control immune response involving cytokines. Do we really want a “strong” immune system?!]

    We want an immune system that is effective and healthy and does what it’s supposed to do. A strong immune system can make us sick by attacking normal cells, so of course we want it to be effective and accurate as well as strong.

    I think that goes without saying.

  28. Harriet Hall says:

    pec,

    You are confusing “predisposing factor” with “underlying cause of disease.” If you only treated the inflammation, the existing cancer would still be there. You have to treat the cancer too. Treating the inflammation would only help prevent new cancers.

  29. pec says:

    [You are confusing “predisposing factor” with “underlying cause of disease.” If you only treated the inflammation, the existing cancer would still be there. You have to treat the cancer too. Treating the inflammation would only help prevent new cancers.]

    You are intentionally missing my point. Killing the cancer cells does not seem to always be the best approach or adequate. However, that is generally the focus of mainstream treatments. Maybe trying to find the cause of the chronic inflammation would be a better strategy, rather than continually developing new chemical poisons.

    I think we know that the typical American lifestyle can be a cause of chronic inflammation, and of metabolic syndrome. It is probably mainly alternative researchers who consider these to be important in searching for causes and cures for cancer.

  30. Harriet Hall says:

    Pec,
    You keep confounding treatment and prevention. We all recognize that it is better to prevent a disease, and we all agree that reducing inflammation is a laudable goal, but once a cancer has developed you have to either kill the cancer cells or control their growth by some means. Do you have any evidence that treating inflammation is an effective way to treat cancer?

    I’m glad you qualified “It is probably mainly alternative researchers who consider these to be important in searching for causes and cures for cancer.” with the word “probably.” Because that is clearly not true. That’s just something you imagined or wanted to believe. Dr Gorski explained that “the study of the immune system and the development of immunotherapies have been one of the major strains in cancer research for decades now.” I’m sure he could cite any number of mainstream science studies to support his claim. What research have the alternative researchers done?

  31. David Gorski says:

    You are intentionally missing my point. Killing the cancer cells does not seem to always be the best approach or adequate. However, that is generally the focus of mainstream treatments. Maybe trying to find the cause of the chronic inflammation would be a better strategy, rather than continually developing new chemical poisons.

    Once esophageal cancer has developed, it is too late. The damage is done. The cancer is there, and treating inflammation will not treat the cancer. It’s been tried before. In general, it hasn’t been successful. Treating inflammation is only good at preventing some cancers.

  32. pec says:

    I didn’t say you should treat the inflammation after cancer has developed. I said it might be helpful to think about what may be disrupting a system that has chronic inflammation. Why and how does the modern lifestyle tend to damage the system to the point that chronic inflammation, metabolic syndrome, type 2 diabetes and artery disease are a likely result?

    I am not just talking about prevention. I am saying that it might be a good idea to look at these diseases from a systemic perspective and try to understand what’s going on. Instead the focus has been on finding better ways to kill cancer cells without killing too many normal cells. The substances used further damage and weaken the system.

    You keep saying cancer researchers already think about all that. But the focus is still on killing cancer cells, and the mainstream treatments are still mainly surgery, radiation and toxic chemicals.

    Gorski’s post is all about how to fight cancer cells, with nothing about the possibility of addressing underlying causes.

  33. pec says:

    And, of course, when you talk about treating inflammation you mean prescribing anti-inflammatory pharmaceuticals. But I obviously meant that chronic inflammation is a result of some kind of disorder of the system as a whole, and that the general disorder is what you should be thinking about.

    What might be the causes of the over-reaction of the immune system in cases of chronic inflammation? You keep mentioning esophageal cancer, because that is obviously not the kind of inflammation I have been talking about.

  34. daedalus2u says:

    pec, the cause of the chronic inflammation is low NO.

  35. Harriet Hall says:

    pec said, “And, of course, when you talk about treating inflammation you mean prescribing anti-inflammatory pharmaceuticals.”

    Actually, that’s not at all what I meant. Or at least what I thought I meant. Pec continues to claim a psychic ability to know more about what goes on in my head than I’m conscious of. Silly me, I thought I was talking about trying to understand what caused the inflammation in the first place and target the cause rather than trying to cover it up with drugs. But pec probably thinks that’s impossible because mainstream medicine treats symptoms while alternative medicine treats causes. [Straw man alert]

    I should stop writing and just let pec write my posts, since she is the only one who knows what I REALLY mean.

    Dr. Gorski’s post was all about fighting cancer because that was the subject of his post. That doesn’t mean that he isn’t even more concerned about addressing underlying causes. Every doctor I have ever known would far rather prevent disease than treat it.

  36. pec says:

    “pec, the cause of the chronic inflammation is low NO.”

    I had a suspicion you would say that daedalus2u. But what is it about the typical unhealthy modern lifestyle that causes low NO? In my opinion, one of the biggest and most widespread dangers in the modern lifestyle is lack of physical exercise. Do you have any ideas about how lack of exercise might contribute to low NO, and whatever else causes and/or goes along with it?

  37. daedalus2u says:

    Exercise increases NO because higher blood velocity causes increased shear on the inside of blood vessels which causes the release of NO. That NO causes those vessels to dilate, and that balance between blood velocity, NO release and vessel dilation is what regulates the normal vascular tone.

    A diet rich in green leafy vegetables increases NO because green leafy vegetables contain a lot of nitrate (a few thousand ppm). That nitrate is well absorbed, is concentrated 10x on the tongue where it is reduced to nitrite by commensal tongue bacteria. That nitrite is swallowed and is reduced to NO in the stomach. The NO/NOx from this route has been shown to have systemic NO effects.

    Meditation and any kind of stress reduction does tend to increase NO levels too. That can be pretty hard for some people to do, I can’t meditate at all. The “best” types of stress reduction mediated NO increases involve social activities because lots of social pathways use NO as a neurotransmitter. But social activities that increase stress would lower NO not increase it.

    Then there is my favorite hypothesis of bathing practices, where in “the wild”, a biofilm of ammonia oxidizing bacteria develops on the skin and ammonia in sweat is rapidly oxidized by them into NO and nitrite which is rapidly absorbed. Bathing removes these bacteria faster than they can regrow. This hypothesis is discussed in a chapter in this book on the hygiene hypothesis (in press)

    http://www.springer.com/birkhauser/biosciences/book/978-3-7643-8902-4?detailsPage=toc

  38. pec says:

    Thanks daedalus2u. So that does help explain why the modern lifestyle can lead to chronic inflammation (which in turn can lead to cancer). So the next question would be — can anything be done to the low-NO system of this type of cancer patient that would help restore their system to normal? Rather than trying to kill the cancer cells (and lots of normal cells in the process), maybe it would make more sense to address the underlying systemic disruptions which were caused by inactivity, low-veg diet, too much bathing, etc. Do you have ideas about how to do that?

  39. daedalus2u says:

    The only thing that will work is prevention. You have to prevent the inflammation from happening because once it does happen, it causes damage and that damage is irreversible.

    Much of the inflammation is secondary to capillary rarefaction due to increased spacing of capillaries due to low NO.

    http://daedalus2u.blogspot.com/2008/10/role-of-low-basal-no-in-capillary-and.html

    This increased spacing causes chronic hypoxia, but with low NO, the regulation of the cell cycle under conditions of hypoxia (as with p53) does not work as well, so cell division happens when cells don’t have the metabolic resources to do it properly. I think that is a mechanism for DNA deletions, and if the p53 gene gets deleted, then the resulting cells are quite resistant to hypoxia.

    As the chronic low NO causes capillary rarefaction and the resulting chronic hypoxia for the cells too far from a capillary, the result is chronic inflammation as those cells die (either by apoptosis or necrosis), spill their cytoplasm into the extravascular space, and cause the chronic inflammation. I think that this is also one of the primary mechanisms for autoimmune sensitization. Normally cell contents such as mitochondria are never exposed to antigen presenting cells. Chronic inflammation can increase that exposure both by cells dying, but also because chronic inflammation causes oxidative stress which reduces the efficiency of autophagy, so that the recycling of organelles such as mitochondria and some neurotransmitter receptors is less efficient and undigested bits get exocytosed into the extravascular space where the immune system can get sensitized to them. Inflammation tends to increase autoimmune sensitization too. I think this is the mechanism for autoimmune sensitization in primary biliary cirrhosis and stiff person syndrome. Often the sensitization occurs late in the disease, implying the autoimmune sensitization is not causal.

    But as far as cancer goes, you have to prevent it. Once there are cells without the proper genetic controls on their growth, those cells have to be removed either by surgery, or by chemotherapy, or by radiation.

    Increasing NO after cancer cells are present may not help, it may make things worse. Many growth factors have effects mediated through NO, NO is an anti-apoptotic compound. More NO may (or may not) stimulate the growth of some tumors. Estrogen does stimulate the growth of some breast cancer cells. Estrogen does activate nitric oxide synthase and that may be the mechanism by which estrogen increases the growth of some cancer cells. NO from estrogen does increase angiogenesis. More angiogenesis may help (by making tumors less hypoxic and so more sensitive to chemotherapy and radiation) or may hurt by increasing their blood supply. It may do both in the same tumor in different regions.

    I think this is why most CAM treatments completely fail for cancer. The raising of NO by the placebo effect may have no effect on tumor cells at all. Certainly once a tumor gets beyond a certain size (less than 1 cm), NO from the outside can’t have much influence on it. Cancer is one thing that I think my bacteria are not going to be especially good for. They should work to prevent it. To treat it, the cancer cells have to be removed.

  40. pec says:

    “To treat it, the cancer cells have to be removed.”

    But do you really think that is practical, in most cases? The mainstream treatments are so damaging to the system, I would expect it would become even more vulnerable to cancer. There would be a vicious cycle — as you try harder to kill cancer cells, the entire system becomes more cancer-prone. Do you agree?

    I am not talking about early stage cancer, because we don’t know if these patients would ever have become sick. If they receive the mainstream treatments they can be cured, or apparently cured. If their system was in the state you describe, the cancer would return — right?

    So according to your explanation, the sort of cancer that results from poor lifestyle and chronic inflammation is incurable. Therefore, the mainstream treatments don’t, usually, work on those cases.

    Do you see what I mean?

  41. daedalus2u says:

    No, that isn’t what I said. The cancer is incurable by removing the conditions that caused the cancer to occur (the chronic inflammation). The cancer can be cured by removing the cancer cells themselves. If you get lung cancer after 30 years of smoking, stopping smoking won’t cure you. If you get cancer after 30 years of chronic inflammation, stopping the inflammation isn’t going to cure you either. You have to stop the inflammation as soon as possible. You don’t have to delay getting cancer for ever, just until you die of something else.

    If there were “magic bullets” that removed each and every one of those cancer cells without damaging non-cancer cells, then after those cells were removed, preventing inflammation would reduce the incidence of a new cancer happening. The incidence wouldn’t go to zero, and likely wouldn’t go to the pre-inflammation exposure condition because there is likely sub-clinical damage to cells subject to inflammation.

    If the DNA for repair enzymes is damaged, then DNA repair will be less robust and damage will accumulate at a faster rate. When the damage to DNA turns on or off the “right” gene, then cancer happens.

    Cells that have been subjected to chronic inflammation are already more susceptible to cancer. Damaging them some more may increase that, but until someone comes up with actual “magic bullets”, there isn’t much else that can be done.

    Damaging adjacent cells with radiation treatments may cause them to become cancerous in 20 years. If the cancer is going to kill you in 2 years, it is a no-brainer to get the treatment.

  42. pec says:

    If a patient is diagnosed with early cancer, of the type you are describing, they probably had low NO and chronic inflammation for a long while before the diagnosis of cancer. So Gorski would “cure” them with surgery, radiation, chemo. But the cause of the low NO and chronic inflammation would probably remain (unless the patient were somehow convinced to radically change their lifestyle, and the MDs here have told us that is seldom possible).

    Ok, so Gorski’s early cancer patient is cured, but the systemic problem remains. So the cancer will probably recur within 5 years — right? So the patient would not actually be cured of the disease. Unless of course they never had cancer in the first place, just some contained cancer cells.

  43. daedalus2u says:

    No, it is not “early cancer”, it is cancer. Gorski doesn’t “cure” them, he cures them. If there are no replicating cancer cells remaining, that is a cure. If a new cancer develops, that is a new cancer, not a return of the old cancer.

    If the cause of the low NO is not corrected, then yes there will be ongoing inflammation and ongoing continued damage. Depending on the tissue compartment affected, there may be little left that can become cancerous. For example, if 90% of the remaining breast tissue is removed, there is only 10% left that has the potential to become cancerous. Cells becoming cancerous is a stochastic probabilistic problem. It is the product of the time, the number of cells and exposure to what ever the carcinogenic agent is. Remove the susceptible tissue and cancer can’t happen.

    Lifestyle changes of exercise, diet and stress relief are not (in my opinion) the most important factor in NO physiology. The most important is ammonia oxidizing bacteria on the skin.

    I think the reason that lifestyles associated with good health are so difficult for people in bad health to adopt is because the “cause” of the difficulty is the bad health, and the “cause” of the ease with which healthy people adopt a healthy lifestyle is because they are healthy. People have the cause and effect mixed up.

    This is a subtle and to some people counter-intuitive point. I see food choice as under physiological control to regulate the state of oxidative stress that the organism is in. Under a state of high oxidative stress, the organism will choose to eat food devoid of antioxidants to spare the metabolic resources to destroy them.

    The observation of diet with cancer and heart disease are all retrospective. The diet is always self-selected. All the large double-blind placebo controlled studies of supplemental antioxidants have all shown no positive health effects. This is in contrast to all of the diet studies which have shown very robust health effects. My hypothesis is that food choice is under phsyiologic control (which we already know), and that the reason food choice is so difficult for people to change is because their bodies are telling them to eat that stuff to remain healthy.

    What the body considers “healthy” is not the same as what individuals may wish. The physiological control of food choice evolved, and so the type of “health” it is trying to maintain is the type of health that evolution selects for, survival and reproduction based on myriad inputs. When those physiological signals are screwed up, then what physiology is telling the organism to do may be counter productive.

    I think that is what happens when people become morbidly obese. The signals that tell them to eat and to stop eating are messed up. NO is a major player in those signaling pathways and when it is low many stress pathways are triggered. Eating is a common stress response and in evolutionary time was a good idea. Now it is a bad idea because the NO signal to turn off eating doesn’t happen and so people eat until they become morbidly obese. They can’t help it because they feel like they are starving. It is very difficult to starve yourself when there is abundant food available.

  44. pec says:

    No, an unhealthy lifestyle is not mostly caused by bad health. Maybe some of the time, but most of the time it is learning and habit. Children see their parents being sedentary. Their parents drive them to school because it isn’t safe to walk. There is no outdoors play time at school because it isn’t safe, or the teachers don’t exercise and don’t see why the kids should. Kids don’t ride their bikes because of all the traffic. Families in the suburbs have to drive everywhere. Our society has evolved in such a way that exercise is inconvenient and is not a normal part of life.

    People don’t feel stupid about not exercising because their friends don’t either. Not long ago not having to walk was a status symbol, and that idea has not died out. Walking is low status, and so is bicycling. What you can’t afford a car? You must be a low life.

    The dietary aspect starts as learning and habits, but can evolve into carbohydrate addiction. I agree with you that a morbidly obese person probably can’t help overeating because the carbohydrate addiction makes them feel hungry when they aren’t.

    Carbohydrate addiction can be broken by completely avoiding carbohydrates for a while, which was the point of the Atkins diet.

    You seem to be saying that patients have valid reasons for sticking with their unhealthy lifestyles, and I don’t really agree. I think it’s mostly the influence of society, and inertia.

  45. pec says:

    “If there are no replicating cancer cells remaining, that is a cure. If a new cancer develops, that is a new cancer, not a return of the old cancer.”

    That is just a matter of terminology. As I keep saying, a person can have cancer cells in their body, yet not be sick with cancer. This is known and accepted. You state with certainty that removing the cancerous cells cures the disease, and is the only way to cure it. But how do you know? Why does a healthy body with a healthy immune system destroy cancer cells constantly? We all have cancer cells but we don’t all have cancer. How do you explain that?

    And why does it sometimes happen that a tumor disappears? Why is the body sometimes (although rarely) able to defeat cancer?

    Your certainty doesn’t seem to be grounded in logic or evidence. I think you just want to support the status quo, even though your own theories are somewhat holistic. You think about how the entire system can get into a vicious cycle and become vulnerable. Most mainstream researchers don’t seem to think in that way.

  46. pec says:

    “And why does it sometimes happen that a tumor disappears? Why is the body sometimes (although rarely) able to defeat cancer?”

    I have to clarify this — I meant that sometimes a large tumor disappears. Small ones, and individual cancer cells, are destroyed by the immune system routinely. And when I said the body rarely defeats cancer, I did not mean early stage cancer, which the body may defeat and contain all the time. So, daedalus2u is claiming that cancer (however exactly he defines it, and of course it has more than one meaning) can be cured by the mainstream treatments, and that it can only be cured by those treatments.

    There is a contradiction in what he is saying. Does a person have cancer if their body contains cancer cells? If so, than many or most of us have cancer. Or does a person have cancer if their system is disrupted in some way which causes chronic inflammation which results in cancer cells which the immune system is unable to contain or destroy?

    By the second definition, killing cancer cells would not solve the underlying problem.

    And why is daedalus2u so absolutely certain that correcting the system (if that were ever possible) would not allow the body to destroy or control the cancer cells, as it would normally?

  47. daedalus2u says:

    pec, We don’t really know what a “healthy lifestyle” actually is because there are no prospective controlled trials of it. There are assumptions that because there is observed a very robust association between good health and diet choice, that diet choice causes good health. That is an assumption that doesn’t have good data behind it. The data that there is better fits the hypothesis that diet choice is determined by health, rather than health is determined by diet choice; interesting that you accuse me of supporting the “status quo”, when I disagree with the conventional wisdom (which you agree with) that a healthy diet causes good health.

    The data fits the hypothesis that diet choice is determined by health better than the hypothesis that it is simply laziness or stupidity, or indolence or bad habits or carbohydrate addiction. That hypothesis explains why it is difficult for people to change their dietary habits in some ways, but not in other ways. There is very good data that supplemental nutrients beyond normal dietary needs don’t improve health. If health is not affected by a change in dietary nutrients, then dietary nutrients are not controlling that health at all. .

    I don’t know what you mean when you say “carbohydrate addiction”. Could you define it, tell me what the symptoms are, tell me how to diagnose it? Humans have an absolute need for carbohydrate. Carbohydrate can be synthesized from amino acids, but that puts a higher metabolic load on the liver and kidneys. The liver and kidneys are among the first organs to fail in the metabolic syndrome. Putting more metabolic stress on those organs would seem counter productive.

    All parameters of physiology are controlled. That means there is a physiological control system that regulates that parameter and increases it when there is too little, and decreases it when there is too much. Obesity is a control setpoint problem. That setpoint has to be set by feedback control. If the setpoint calls for more eating, it will be difficult or impossible for an individual to not eat.

    Yes, it is a matter of terminology. When discussing things it is important to use the correct terminology so that ideas are expressed and understood unambiguously.

    I think you are mistaken. People can have cancer cells in their bodies and appear to be healthy because the number of cancer cells is too few to cause overt symptoms that can be diagnosed. This is not the same as “not being sick with cancer”. If they don’t have overt symptoms, all that can be said is that they don’t have overt symptoms. That is why real doctors don’t talk about cancer “cures”, they talk about X year survival rates. If you survive until you die from something other than the original cancer, then you have been “cured” even if there are still cancer cells in your body when you die.

    Why some tumors don’t progress is a good question, for which there are probably many answers depending on the tumor and the individual. We know some of the answers, there are many genes that regulate the division of cells, and some of them act as off switches (such as p53). When the DNA that codes for those off switches gets deleted, then the cell can replicate out of control. This stuff is very well known by main stream cancer researchers.

    Real cancer researchers are very much aware of the limits of the techniques they are using. They would very much like to have better methods, but they will adopt new methods only after they have been shown to be better. The reason for this is because they don’t want to risk giving real patients with real cancer treatments that might be worse.

    There are no “good” cancer treatments. There are only treatments that are less bad than doing nothing. When better treatments have been exhausted and all that are left are treatments that are worse than doing nothing, then treatment should stop.

  48. pec says:

    “interesting that you accuse me of supporting the “status quo”, when I disagree with the conventional wisdom (which you agree with) that a healthy diet causes good health.”

    Sometimes I agree with the status quo, consensus, opinion, and sometimes I disagree with it. According to what I know, eating junk food causes poor health, not the other way around. Diet is mostly culturally determined, in my opinion. Maybe you are correct, to some extent, but I think you are wrong in saying poor health leads to eating junk food.

    [I don’t know what you mean when you say “carbohydrate addiction”. Could you define it, tell me what the symptoms are, tell me how to diagnose it? Humans have an absolute need for carbohydrate.]

    The danger is in eating too many refined carbohydrates — white sugar and white flour, etc. The body does not know how to process junk food, and it can lead to insulin resistance and eventually type 2 diabetes. Refined carbohydrates can be addictive — this is well known and accepted (not necessarily true, but it seems to be).

    According to alternative medicine, which you probably don’t agree with in general, our immune systems routinely destroy cancer cells and/or prevent them from spreading. So a perfectly healthy person might have cancer cells in their body. It is not the same as having cancer as a disease, where the immune system cannot control the cancer cells.

    Very often, it seems to me (and alt med in general), early cancers that are “cured” by mainstream treatments were not cancer at all, in that there was no disease condition present. If there were, the cancer would have recurred after the treatment, because there is nothing about the treatment that addresses the actual disease condition.

    “Real cancer researchers are very much aware of the limits of the techniques they are using.”

    No, not always. Gorski is very proud of his success at curing at least some forms of cancer. We had arguments at this blog and he claims a high success rate, using the mainstream treatments only.

    “When better treatments have been exhausted and all that are left are treatments that are worse than doing nothing, then treatment should stop.”

    Yeah, but they don’t always know when to stop. I know of a patient being tortured with chemotherapy even though she has advanced incurable liver cancer. I guess they’re trying to prolong her life by a couple of months.

  49. daedalus2u says:

    pec, as I recall, Dr Gorski doesn’t talk about “curing” patients, other than as short hand for X-year survival rate. He is very aware of the difference, and I think that I can always understand what he is meaning and it is always X-year survival rate, or some other objective finding that can be unambiguously determined; as in a person is either alive or not at a certain date, the absence of growth of tumors, the absence of tumor markers, the absence of leukemic cells in the blood, rather than a nebulous and undefined notion of “cure”.

    What you call alternative medicine doesn’t have methods for diagnosing cancer, early or late (which terms are ambiguous). They don’t describe a mechanism by which the immune system destroys cancer cells, they don’t have a mechanism by which their alternative treatments stimulate the immune system, they don’t have a way to measure how much stimulation of the immune system they are producing, they don’t have a way of modulating a dose-response immune system stimulation and they don’t describe mechanisms by which the now-stimulated immune system destroys cancer cells.

    Diabetes type 1 is caused by the immune system ablating the islets in the pancreas. Stimulating the immune system with alternative medicine might be expected to increase the incidence of diabetes (if that alternative medicine was actually stimulating the immune system). Inflammation is caused by the immune system. Stimulating the immune system would be expected to exacerbate inflammation, and also exacerbate autoimmune disorders.

    All the proponents of alternative medicine have done is assert that their treatment work by stimulating the immune system, even though there is no objective data that suggest any stimulation occurred, or that any such stimulation was responsible for killing tumor cells, or even that the alternative medicine treatment had any positive effects. There is objective data on conventional cancer treatments. That is how conventional cancer treatments are developed and used, with objective data as benchmarks. Alternative medicine never uses objective benchmarks for something like cancer treatment.

  50. pec says:

    You are making generalizations about alternative medicine that have nothing to do with reality. You probably haven’t read the theories of any alternative medicine researcher. There isn’t just one alternative theory of cancer — holistic medicine is a general approach, and each researcher has their own ideas. So how can you make encompassing statements that supposedly cover all of them?

    “Diabetes type 1 is caused by the immune system ablating the islets in the pancreas. Stimulating the immune system with alternative medicine might be expected to increase the incidence of diabetes”

    That statement makes no sense at all. We want the immune system to be healthy, not to go on an rampage destroying the body. The immune system can be over-active or under-active, can go wrong in many ways. No holistic medicine practitioner has a goal of making the immune system over-active and creating auto-immune disorders!

  51. pec says:

    daedalus2u,

    And I have said many times that I don’t advocate any particular alternative cancer treatment or theory. I am criticizing the mainstream approach, because its success and value are often taken for granted. Many mainstream cancer researchers seem to believe they are on the right track, and that continuing their approach will lead to success.

    If chronic inflammation often leads to cancer, that seems to suggest that cancer may be a disorder of the entire system. Yet the conventional view seems to be that an otherwise healthy body is attacked by cancer cells. The alternative, holistic, view is that healthy bodies get cancer cells but are able to destroy or control them.

    The conventional view of cancer is based on the infectious disease model, and has resulted in the current treatment methods.

  52. riley290 says:

    I applaud you lasting as long as you have trying to straighten out the nonsense of pec.

    Pec, you make a very wise statement here; “how can you make encompassing statements that supposedly cover all of them?” You should do around a year more of research and then come back with your ideas. You will make far less errors in reasoning and logical fallacies.

    As a short aside, you argue that medicine doesn’t try to discover and treat inflammation but I would direct you possibly the Journal of Inflammation, the Journal of Inflammation Research, Mediators of Inflammation, The Open Inflammation Journal, Inflammation Research, European Journal of Inflammation, ok I think I’ve made my point.

    You show a completely myopic view of the research going on in regards to cancer, which is being looked at by more fields of research than you can even name. Go ahead and google every field involved in cancer research and prevention and list them, I bet you miss at least 15.

    Also, statistics and immune subjects would be good fields to get a better grip on the issues that you are attempting to talk about.

  53. riley290 says:

    Wow, also look into the “infectious disease model” and give me a good definition, I think you have the most limited idea of what it is. Start with Koch’s postulates and then once you understand the historical tenets you only have 120 years of literature to search through to get an idea of what you’re trying to talk about.

    I don’t understand how you can say that the conventional view doesn’t support the fact that many individuals get cancer and or dysplastic growths but never become metastatic or a mass issue. This is a well recognized fact.

    I’ll suggest you start your research of cancer with the Greeks as they documented very well the occurrence and gross anatomy of tumors from autopsies. They surely dealt with the “modern lifestlye” problem.

    Once you follow that through then start to look at all of the different conditions that cause cancer. What about cancers that arise due to single base pair mutations? What about fetal and childhood cancers? How about cancers that are caused by virus infections? Lifestyle?

    It is very arrogant to think that the 20th century brought about cancer. It has existed far before either you or I or any of the predecessors of our beliefs walked the earth and the cure will be found by investigating these ancient biological roots. Our lifestyle may have increased the rate of cancer but I would also argue that the massive increase in life expectancy from bb 50 to bb 80 in a short 40 year time span had a little bit to do with the increase.

    I mean just how many cancers are in adults older than 50? Do you know because I know the best estimates we have and its a whole lot. Have you considered that in 1950 these weren’t cancer cases because the majority population in that age group was dead.

    Your view that the medical community is not trying to give every approach a reasonable run-out is far misguided. You can look through PubMed or Google Scholar with whatever search query you have about cancer and you can find your studies. These arguments that the medical establishment isn’t “looking at all approaches” is old and it is because you either recycle old ideas that have been bunked when researched or make claims that have no reasonable basis to even bring merit.

    I applaud your effort to try and bring a different view but consider this; it is insulting to those who spend a career trying to cure some aspect of these horrible diseases to hear their efforts be dismissed like this. We don’t just pick some aspect and say “oh, that’s interesting to look at and talk about”, from the time you get out of undergraduate you have synthesized enough knowledge to know if your efforts of a career will bear any fruit. Don’t disrespect the fact that people do more than write on the internet about cancer.

  54. pmoran says:

    “If chronic inflammation often leads to cancer, that seems to suggest that cancer may be a disorder of the entire system. Yet the conventional view seems to be that an otherwise healthy body is attacked by cancer cells. The alternative, holistic, view is that healthy bodies get cancer cells but are able to destroy or control them. ”

    Actually cancer is a very rare and very late consequence of chronic inflammation, and invariably a *localised* inflammatory process is responsible, such as a chronic venous ulcer or parasitic infection of a particular organ.

    ” The alternative, holistic, view is that healthy bodies get cancer cells but are able to destroy or control them. ”

    This is a simplistic, even metaphorical, description of very complex mechanisms. Does inheriting a BRAC or P53 gene defect make one “unhealthy”, and what can be done to make such a person healthier?

    Also, once progressive, invasive cancer has developed these systems can be known to have failed. They can sometimes be reactivated by certain technologies, but no alternative method is known to do so.

  55. daedalus2u says:

    pec, the successes are not “taken for granted” they are measured. Progress has been made in prolonging the lives of many individuals that have been diagnosed with cancer. Cancer researchers are making progress.

    What progress are alternative medicine practitioners making?

    It has been said that perfect is the enemy of good. Are you saying that patients should forgo a good remedy while waiting for a perfect one? Do you have any basis other than wishful thinking that alternative medicine will ever lead to that perfect cure?

    Can you name a single alternative treatment that has been demonstrated to work better than the standard of care conventional treatment? No you can’t; because if an alternative treatment was shown to work better than a conventional treatment that alternative treatment would become the new standard of care.

  56. David Gorski says:

    Actually cancer is a very rare and very late consequence of chronic inflammation, and invariably a *localised* inflammatory process is responsible, such as a chronic venous ulcer or parasitic infection of a particular organ.

    Actually, I’d beg to differ that cancer is a “very rare” consequence of chronic inflammation, although it is certainly a late consequence. Barrett’s esophagus, for instance, is not uncommon. There’s also a link between angiogenesis and inflammation that ties into cancer during its progression. See:

    http://www.nature.com/nature/journal/v454/n7203/full/nature07205.html

    http://www.nature.com/nature/journal/v420/n6917/full/nature01322.html

    http://www.nature.com/nature/journal/v457/n7225/full/457036b.html

  57. pmoran says:

    I have no doubt cancers provoke inflammatory and repair responses once developed. We surgeons can often observe those macroscopically.

    But I can think of a lot of chronic inflammatory processes where cancer of the involved tissue is extremely rare and a lot of cancers where there is no reason to suspect any such prior event. I cannot yet see it as a fundamental process in cancer development, as opposed to facilitating growth, spread or metastases.

    But you are closer to all this than I.

  58. pec says:

    [Does inheriting a BRAC or P53 gene defect make one “unhealthy”, and what can be done to make such a person healthier?]

    I have said, repeatedly, that I realized there are many types of cancer. In this context I was talking to daedalus2u, who says that some types of cancer can be the result of chronic inflammation. I also know that chronic inflammation may lead to artery disease and type 2 diabetes. My point was that it seems that certain types (not all types, certain types) of cancer seem to be another of the lifestyle disorders. These disorders involve the immune system, and the system in general. That is the approach of holistic medicine, which tends to consider the system as a whole. As opposed to mainstream medicine, which tends to be reductionist and to focus only on certain parts of the system.

    The infectious disease model of cancer says that the goal is to eradicate the cancer cells. Cancer cells as seen as being the disease, not a result of a larger disorder (see Harriet Hall’s comment).

    Yes I realize there are many different mainstream researchers with many different ideas, just as there are many different alternative researchers with different ideas. But there is a general difference between the two approaches.

    I realize that no one, either mainstream or alternative, has discovered a cure for cancer. My point is that the current mainstream approach might not be the most promising. It certainly has had more money poured into it than the alternative approach, and I think many experts would agree with me that the results have not been encouraging.

  59. daedalus2u says:

    pec, can you give us a specific example of what an “alternative approach” would be, and a specific example of what money should be spent doing research on? In particular, by what mechanism(s) are those treatments more holistic?

  60. riley290 says:

    You have yet to come close to even summing up the research that has gone on in cancer. You have no clue what the “mainstream” approach is so I fail to recognize how you have the capability to distinguish meaningful from non in this field of research.

    There are too many people out here that know what they are talking about and work daily for cures on this disease. You are not one of them and you should start listening to those who do more than read the internet and parrot bad arguments they’ve read.

  61. pec says:

    “pec, can you give us a specific example of what an “alternative approach” would be”

    I said, over and over, that holistic medicine is much more likely to consider the whole system, and to consider many interacting variables. The study of complex systems originated and evolved within holistic science, not in mainstream science. If you are a cancer researcher and you believe the cancer cells are the disease (and Harriet Hall said that is what is currently believed), and your goal is to kill cancer cells, then you are not approaching the problem in terms of complex systems. If you believe the cancer cells are the disease, period, then your approach will be simplistic and reductionist.

  62. pmoran says:

    Pec, that is positing mystery where none exists. Most cancers are clearly localised processes that can sometimes be subject to systemic influences (e.g. hormonally sensitive breast cancer).

    It is also humbug, the kind of vacuous promotional material beloved of the alternative cancer industry. When it is not pushing supposed cancer-killers itself, such as Laetrile or Hoxsey, holistic medicine centres around highly simplistic and frankly disproved beliefs that cancer can be cured by fiddling with the diet, adding a few supplements, Detox, and thinking about it. I have seen it all.

  63. Harriet Hall says:

    Medical science has two goals: treating the cancer AND preventing disease. Killing the cancer cells does not imply that we don’t keep trying to understand the factors that allowed the cancer to develop.

    If you have a forest fire, you put out the fire first. The fire is the immediate problem. By pec’s reasoning, the problem is not the fire, but the unhealthy forest that allowed a fire. Of course, you try to figure out how the fire started and you try to use that knowledge to prevent future forest fires. The fire is the “disease” and the forest conditions were what allowed the “disease” to develop.

    Scientific medicine considers the whole system and many interacting variables. The concept of complex systems was developed by mainstream science and only later co-opted by “holistic medicine.” Ecology is mainstream.

  64. daedalus2u says:

    pec, If you ignore the cancer cells (as you seem to be doing), how can that be considered holistic? What is “holistic medicine”? What are some specifics, other than just using the word “holistic”? Is there any data about it, or is it just a philosophy?

    In looking up holistic medicine on the web, I found a course where one could get a BS, MS, and PhD in holistic medicine by mail (after paying $10k+). In the study materials, there was no physiology, no immunology, no hematology, no endocrinology, just things like reflexology, iridology, crystal healing, and magnet healing.

    If it is “holistic”, how can it ignore aspects of medicine which are well known except by denying that they are important? It can’t be considered holistic by considering stuff likely to not be important while ignoring stuff that is known to be important.

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