Cancer and genes: Have we got it badly wrong?

By Jerome Burne

Professor Mina Bissell presents a fascinating challenge to the cancer establishment. She is a highly respected academic and leading authority on breast cancer at the University of California, where she is Distinguished Scientist with Lawrence Berkeley National Laboratory’s Life Sciences Division next to UCB campus.

For the last 30 years she has been working on a radical theory about cancer that until recently put her right outside the mainstream. ‘The dominant cancer theory,’ she said in a TED talk a couple of years ago ‘stated that a single oncogene (a gene that can trigger cancer) in a single cell leading to tumours could make you a cancer victim.

‘This has never made sense to me. We have trillions of cells and if even a tiny fraction had a cancerous mutation you would rapidly become a lump of cancer.’ Her studies in the 1980s showed that if a potent oncogene for chickens, (the first such gene was reported in 1911 by Rous), was injected into chick embryos, the oncogene could be expressed and be activated, but the infected cell could form part of a healthy organ because no tumour developed. The implication is that something more than a gene mutation is needed to turn a cell cancerous.

This is not to say that genetic mutations aren’t important but Bissell believes that in focusing almost exclusively on cancer causing mutations we are in danger of missing the forest for the trees.

Need a healthy network

What counts, it turns out, is the health of the network of cells that surround any cells that have cancer causing potential. It’s known as the “extracellular matrix” (ECM) and it’s made up of a dense scaffolding of large, insoluble proteins surrounding almost all tissues, but the exact molecular composition of the ECM for different tissues is different. Blood vessels pipe in nutrients while lymph vessels handle the drainage.

When the ECM is healthy, the cells nestle tightly against each other like terraced houses and any hint of leakage from a cell or abnormal behaviour is quickly dealt with by the neighbours. In areas that are breaking down, cells lose touch with their neighbours, spew waste and grow uncontrollably.

Bissell and other researchers are now convinced that by properly managing a cancer’s local environment it can be contained. ‘We really should be able to control cancer as a chronic but dormant disease, like diabetes’ she says. There is now a whole field of microenvironment, based on work from her and a number of other laboratories such as the Tumour Microenvironment Network at the National Cancer Institute in Bethesda, Maryland.

The idea that what happens in a cell turning cancerous can be affected by its neighbours makes obvious sense, so how come it has been ignored until very recently?

A simplistic view of genes

‘The excitement in the late ‘70’s early 80’s when oncogenes (cancer causing) and the suppressor genes that turned them off were first discovered was so great that some senior scientist still believe the simplistic view that a single oncogene is enough to cause cancer,’ says Bissell. As a result identifying single genes and developing drugs to block them became the standard approach. In an article in Nature magazine many years ago, this approach was compared with trying to reduce the incidence of traffic jams by concentrating all your attention on individual cars.

Widening your angle of vision so you also investigate the conditions in the area surrounding the tumour – the ECM – and the health of the neighbouring cells opens up a whole new approach to the origins and treatment of the disease. It suggests that combining treatments aimed at boosting our immune and energy generating systems with less toxic drugs makes a lot of sense.

It also switches the spotlight to prevention. ‘If we took seriously at all the things that we know can help cancer prevention,’ says Bissell ‘such as tackling obesity, exercising, eating fewer carbohydrates especially sugar, we would have many fewer fully fledged tumours and a reduction in mortality.

‘But if we understood the importance of the microenvironment and the cancer context we could, in some cases, make cancer into a lower risk chronic disease.’

Starve cancer cells of sugar

An example of what she is talking about is cutting back on carbohydrates and especially sugar because cancer cells are well known to need much more glucose than healthy cells, so starving then makes sense. Bissell cautions that once a tumour has developed any such approach should be combined with regular drug treatment.

Early work supports the damaging role of sugar. A paper published by Onodera and Bissell just this past year in J. Clinical Investigation showed that overtly tumorigenic breast cancer cell lines could be “reverted to a quiescent and normal phenotype if glucose (sugar) was removed from the medium in which these were cultivated.”

Cancer cells’ high sugar demand is usually said to be a result of cells turning cancerous. However Bissell has found that a high level of blood sugar (glucose) can itself promotes cancer and what’s more that cutting back on sugar can reverse it.

“More research is needed but a dramatic increase in sugar intake could be a cause of oncogenesis,” she says on the Berkeley Lab website. The change involved a protein called GLUT3, involved in moving glucose into cells, which is found in very high levels in cancerous breast tissue.

Sugar can turn cells cancerous

With the aid of a revolutionary 3-dimensional system her laboratory has developed for analysing cancer cells, Bissell showed that healthy cells became disorganised when GLUT3 production was pushed up. Then damping down GLUT3 in the cancerous cells turned down the genes driving the cancer growth. The result was that the cells became healthy-looking again, even though the cancerous mutations were still there. In other words changes in the microenvironment of cancer cells can change the effect of cancer causing genes.

This research suggests why the high blood sugar levels found in people who are obese or diabetic can increase the risk of cancer.This is the reason why other researchers have become very interested in the ketogenic diet – which involves a major reduction in carbohydrate consumption. More details.

Bissell’s ideas are being picked up by other researchers and more compounds in the ECM are showing up as affecting whether a cell turns cancerous. One of these is a protein known as CD36 which is involved in making both fat and connective tissue but also controls processes that promote healthy breast tissue. Researchers at the University of California, San Francisco found that when CD36 is missing it leaves an environment where cancer is more likely to grow.

But it is not just chemicals in the ECM that can restore cancerous cells to health. Daniel Fletcher, a professor of Bioengineering at Berkeley in collaboration with Bissell’s laboratory found that pressure exerted by cells in the ECM can also produce a reversal of cancer. This involved a new way of studying cells in the lab – the 3D system mentioned above. Rather than squashing them flat on a slide, cancerous cells were held in specially designed flexible silicone chambers.

Cancer cells lost in the big city

Fletcher and his collaborators found that the squeezing had a beneficial effect on a protein called E-cadherin that is involved in keeping cells closely bound together. Breast cancer patients with low levels of E-cadherin have poorer chances of recovery. This doesn’t mean that squeezing tumorous tissue is going to help but it shows the variety ways the micro-environment can affect cancer development. Other ways to increase E-cadhedrin production includes black tea. (Read more.)

“Cancer is not only a problem with growth,” Bissell argues “instead it is a matter of context, which when altered could lead to disorganized growth.’ She makes an analogy with human society. Just as kids from a small town can lose their bearings in in a big city, so cancer cells can find themselves disoriented when their surroundings change. Soon, they are running amok, behaving in ways they never would at home, where their neighbours help keep them grounded.

Other changes to a neighbourhood that can trigger cancer promotion, beside high levels of glucose and a loosening of the bonds between neighbouring cells, includes the oxidants that the body produces in response to stresses.

These in turn send out chemical signals that cause inflammation, which can trigger more changes in a cancerous direction. This is the thinking behind giving anti-inflammatory drugs such as aspirin to help cut cancer risk.

Combination treatments for cancer

Recently Professor Lisa Coussens of the Oregon Health and Sciences University in Portland has suggested that combining therapies such as vaccines, anti-inflammatories and fasting (calorie restriction) is an effective way to reduce the inflammation that’s linked with cancer.

‘But you can’t shut inflammation right down because it is part of the immune response which is crucial to controlling cancer,’ says Coussens. ‘The fact that we don’t all walk around with big tumours is proof that the immune system works most of the time.’

The complicated dance between tumours, inflammation and the immune system show how important the ECM is. For instance, Coussens has found that sometimes immune cells can help a tumour. ‘Macrophages are attracted to tumours under attack from chemotherapy,’ she says. ‘They can toughen it up, making it less vulnerable to the drugs.’

Bissell’s approach shows up the shortcoming of chemotherapy which damages cancerous and surrounding healthy cells alike. ‘It will still be needed,’ she says ‘but it should be combined with other approaches such as signalling inhibitors and antibodies. Also potentially useful would be lowering carbohydrate intake, losing weight if you are obese and exercise. ‘Exercise lowers your chance of recurrence better than most available drugs in a number of cancers,’ she says.

Who will pay for the new treatments?

But moving from the theory of the influence of the ECM to using it as a guide to new and experimental treatments will be challenging. “It’s already accepted by some oncologists, ’she says ‘especially for those working with leukaemia and lymphomas.

‘But it should also be applied to treating solid tumours. Problem is that almost none of this research showing how the microenvironment can affect gene regulation, which goes back four decades, is in the text books.’

The criticism that is always made of the non- standard therapies is that they don’t have trial data to support them. But as Bissell points out: ‘Someone has to pay for the clinical trials to get the data. The drug companies aren’t going to do it, which leaves the government and charities, but science budgets are being cut.

So what should patients do who want to try unconventional sort of approaches ‘For now the best way is combining a wise use of the standard therapies with the non-conventional ones, such as acupuncture, massage, osteopathy.’

Bissell is all too familiar with criticism for advocating non-standard therapies as a way of effecting beneficial changes in the ECS, but she believes it is grounded in solid research. ‘We have made amazing discoveries,’ she says ‘thanks to the support of some heroic individuals within the funding agencies, in my case, for example, the Department of Defense Breast Cancer program, Breast cancer Research Foundation, and we will continue to publish high quality science despite the people who have much narrower visions.’

‘There is so much more to be discovered. There is so much mystery still. I always say to my students – as I said in my TED talk: Don’t be arrogant because arrogance kills curiosity and passion.’

It would be great if her work generated more curiosity than arrogant resistance.

 

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “10 Secrets of Healthy Ageing” was written with nutritionist Patrick Holford. He blogs at “Body of Evidence” – jeromeburne.com. 2015: Finalist for 'Blogger of the Year' award from Medical Journalists' Association.

19 Comments

  • Metabolic derangement, within the mitochondrial DNA, seems to be a serious culprit lately. The work of Drs. Ko and Pedersen, originally at John Hopkins, demonstrated the benefits of using 3-bromopyruvate to inhibit hexokinase II which is critical for anaerobic glycolysis; used exclusively within cancerous cells, even in the presence of oxygen.
    The Warburg Effect might also be a “new” way to attack this scourge upon us.

    • Yes, Dr Mitchell, isn’t it an odd thing that the century old Warburg centric views are returning to be back in fashion? Presumably it was the fat-phobic views generated by Ancels Keys diet-heart hypothesis given over to heart disease that rendered Warburg style views unfashionable? It is a slow process but there exist people who have come to realise that dietary fats are not angiotoxic (not bad for the heart) and there exist several meta-analyses that undermine this false notion that a high fat diet will clog arteries and disrupt the function of the heart.

      Glucose has earned its right to be described as the mother of all biochemicals, because almost all biochemicals must be (ultimately) derived from it. Via the process termed photosynthesis plants harvest energy from photons of light whose source was the sun and that invest that energy into the way electrons forge carbon-hydrogen bonds and hold them. Some while after metabolism breaks those bonds and releases that energy that was invested in those electrons that defined those bonds. It is a quantum effect. ‘Quantum biology’ is normal and as old as life itself, while term just acknowledges science and scientists only just realised.

      Plants and plants, quite naturally are highly tolerant of glucose concentrations in sap, the more the merrier, but the diet-heart idea, a falsehood, has generated mass hysteric lipohobia and promoted high carb eating in humans. Of course carbs are digested to become glucose, and actually glucose in the blood of any species is not well tolerated, which is why the mechanisms exist to manage concentrations of BG, convert glucose to glycogen, or to effect lipogenesis (convert of glucose to fats) under the influence of a hormone called insulin.

      Plants cannot, generally, live for long in the absence of food or water, but there exist large mammals that can release stores of body fat and last for as many as 120 days in hibernation without need of water, providing they retired to bed with enough body fat to get them through. The role of body-fats in animals, end especially amongst mammals gives rise to options and possibilities that are no open to plants. However in animals high concentrations of glucose in blood tend to dehydrate their cells and undermine viability of cells.

      It’s odd to think what a regressive step the diet-heart hypothesis amounted to and the extent to which it persists, given the complete absence of evidence to support it. Complex life requires more complexity biochemistry. Glucose remains essential, but the simplest biochemistry that most closely associates with glucose, in itself, can only support simple lifeforms typical of the chloroplasts. We humans are a cut above chloroplasts, many of us anyway.

      • Good post. I think more people are beginning to realise how much harm science/medicine has done and does because it is basically a profit-driven industry sourced in the erroneous belief that everything can be reduced to the material and the mechanical.

        While there is no doubt that science/medicine has gained enormous detailed knowledge of body function, this knowledge is distorted because it is viewed from the materialist reductionist perspective.

        And because science/medicine is locked into this perspective and because it is profit driven and influenced if not at times controlled by vested agendas whose sole focus is profit, enormous profit – pharmaceuticals being the main driver – the distortion is increased.

        While it may well be unconscious and one can believe those working in the fields of science/medicine truly believe they operate from a place of good intentions, in some cases, a belief in noble intentions, the truth is that science is now an industry which provides enormous profits, both financial and prestigious, and medicine is the same.

        In such an environment, ignoring or even denying the huge complexity and enormous levels of ignorance which still exist within science/medicine as to how the remarkable organism of the human body functions, is required, if function is to be reduced to the material so that anything can be addressed by medication. Since, modern (Allopathic) medicine at this point in history has nothing but the knife and/or drug, and the knife, while representing an impressive area of skill in Allopathy, is limited in application, it is therefore the drug which must be found for all disease, real and imagined.

        It is the drug mentality which drives ‘maybe medicine,’ Statins being a classic example, where millions are given medication for a disease they do not have and may never get. While such prescriptions are described as prophylactic and I am sure the scientists and doctors responsible for them believe that this is what they are, the reality is that they are sourced in a need for power – to control the body at all costs, and a need for profit, now that science/medicine is one of the most profitable industries in the world.

        No-one likes to see their profits drop and that means we need more disease, real or invented, and more medications.

        As long as science/medicine treats nature and its wisdom with arrogant disregard I will continue to get many things wrong and utterly fail to understand how the human body works, particularly in regard to the first medicine, food. For no understanding of any value will ever come where the body is seen as a machine and/or bag of chemicals, as one erstwhile scientist has described it.

        Instead, damage and even death are more likely to be the result as scientists and doctors pontificate about diet and push pills to solve every problem.

        The list is growing longer as to how often science/medicine has gotten it wrong in regard to food in general and diet in particular. A good dose of common sense would not go astray for all those employed in the science/medical industry. In the absence of that happening in the short-term, it is a ‘medicine’ which individuals must apply if they are to make their own wise choices.

    • So cancer cells can find themselves disoriented when their surroundings change. Soon, they are running amok, behaving in ways they never would at home, where their neighbours help keep them grounded.

      The word used here is ‘disoriented.’ The word I used was ‘confused,’ in a post I wrote last year but it amounts to the same thing.

      So much of Allopathic treatments, drugs and vaccines, are designed to ‘trick’ the body. The use of ‘imposters’, deception and trickery to force or encourage the body to act ‘other’ that it would normally and naturally do, must have some impact.

      Is there a connection between this and the way cancer can also ‘trick’ the body, manipulate and ‘make’ it do what it would not or should not naturally do?

      When modern medicine sets out to hoodwink the body does it create confusion in our cells which makes it easier for them to be hoodwinked or tricked in general and subject to disease?

      Cancer may trick the body but most of modern medicine does the same thing much of the time. Logic suggests the two may be connected.

      While science/medicine does continue to ask questions and this article is a part of that process, I can only wonder how many make a connection between ‘how cancer acts,’ and how so much of modern medicine ‘works.’

      Given the ancient presence of cancer as a disease there are obviously many triggers but perhaps the massive rise in cancer today, to one in two from one in ten in 1900, is linked to the actions of science/medicine and the pharmaceutical methodology it relies upon to a very large degree. A methodology which did not exist a century ago and which was not used in the way it now is, until probably 60 years ago, must have an impact on the individual human body and its capacity to function.

      In a world of mass medication for diseases people do not have and may never get and often from childhood, the question must be asked: Yes, but what does it do to the body?

      Every action has an effect and subjecting the body to unnatural, artificial substances in the form of medications and processes, designed to ‘trick,’ or to use the word in this article ‘hoodwink’ the body must have an effect which involves confusion. How long does it take an immune system, and no doubt some are more robust than others, to become permanently ‘confused’ and unable to accurately identify Self and Other; Friend or Foe?

      All that interventionist ‘maybe medicine,’ often in the form of experimental, synthesised drugs, may be meddling which, ultimately confuses the body and creates more disease.

      ‘Our bodies produce thousands of different molecular messages, and drug developers have taken advantage of this fact by synthesizing ‘imposter’ messages that mimic the chemistry and shape of our natural molecules. In fact many drugs used in medicine today achieve their results by preventing natural signals from engaging their receptors.’ From Secrets of Your Cells, Discovering Your Body’s Inner Intelligence, by Sondra Barrett, PhD.

      Doctors and patients, who would be horrified to be so ‘tricked’ by those who set out to deceive and who ‘dress’ and ‘act’ and ‘talk’ in recognisable ways and yet are imposters, think nothing of ‘tricking’ their cells and their body consistently.

      https://rosross.wordpress.com/2014/02/26/you-and-your-body-are-in-this-together/

  • This comment touches upon something I have pondered, but in a different way:

    so cancer cells can find themselves disoriented when their surroundings change. Soon, they are running amok, behaving in ways they never would at home, where their neighbours help keep them grounded.

    The word used here is ‘disoriented.’ The word I used was ‘confused.’ So much of Allopathic treatments, drugs and vaccines, are designed to ‘trick’ the body. The use of ‘imposters’, deception and trickery to force or encourage the body to act ‘other’ that it would normally and naturally do, must have some impact.

    Is there a connection between this and the way cancer can also ‘trick’ the body, manipulate and ‘make’ it do what it would not or should not naturally do?

    When modern medicine sets out to hoodwink the body does it create confusion in our cells which makes it easier for them to be hoodwinked or tricked in general and subject to disease?

    Cancer may trick the body but most of modern medicine does the same thing much of the time. Logic suggests the two may be connected.

    While science/medicine does continue to ask questions and this article is a part of that process, I can only wonder how many make a connection between ‘how cancer acts,’ and how so much of modern medicine ‘works.’

    Given the ancient presence of cancer as a disease there are obviously many triggers but perhaps the massive rise in cancer today, to one in two from one in ten in 1900, is linked to the actions of science/medicine and the pharmaceutical methodology it relies upon to a very large degree. A methodology which did not exist a century ago and which was not used in the way it now is, until probably 60 years ago, must have an impact on the individual human body and its capacity to function.

    In a world of mass medication for diseases people do not have and may never get and often from childhood, the question must be asked: Yes, but what does it do to the body?

    Every action has an effect and subjecting the body to unnatural, artificial substances in the form of medications and processes, designed to ‘trick,’ or to use the word in this article ‘hoodwink’ the body must have an effect which involves confusion. How long does it take an immune system, and no doubt some are more robust than others, to become permanently ‘confused’ and unable to accurately identify Self and Other; Friend or Foe?

    All that interventionist ‘maybe medicine,’ often in the form of experimental, synthesised drugs, may be meddling which, ultimately confuses the body and creates more disease.

    ‘Our bodies produce thousands of different molecular messages, and drug developers have taken advantage of this fact by synthesizing ‘imposter’ messages that mimic the chemistry and shape of our natural molecules. In fact many drugs used in medicine today achieve their results by preventing natural signals from engaging their receptors.’ From Secrets of Your Cells, Discovering Your Body’s Inner Intelligence, by Sondra Barrett, PhD.

    Doctors and patients, who would be horrified to be so ‘tricked’ by those who set out to deceive and who ‘dress’ and ‘act’ and ‘talk’ in recognisable ways and yet are imposters, think nothing of ‘tricking’ their cells and their body consistently.

    https://rosross.wordpress.com/2014/02/26/you-and-your-body-are-in-this-together/

  • Thank you for a great article, Jerome. I have shared it on my blog. Inspiring.

  • Yes Jerome, thanks once again for your courage in publishing what may be considered controversial. For the life of me I can’t understand why this isn’t seen as obvious. The analogy of the cells lost in the city is universal in it’s application. Everything is dependent upon contextual parameters. Why would we imagine cancer to be any different. As Bissell said though, who is going to pay for research that concludes the adjustment of contextual parameters is the key rather than just more patented chemicals

  • Great article Jerome, Nina constantly intelligently challenges standard thinking. Modern medicine too often ties people hands behind their backs, disabling the helaing mechanisms that support normal cellular function.

  • “we are in danger of missing the forest for the trees.” Why are you writing in American?

    • Editorial

      You are quite right. It was a direct quote and should have been indicated as such. Thank you so much for noticing.Do hope no one else was confused or stylistically irritated.

      • I missed it but not sure why it constitutes American.

        • Because in British English the expression uses “wood” not “forest”.

          • Ah, fair enough. In Australia it is interchangeable.

          • Editorial

            Gosh you are someone who likes to keep their nose firmly pressed against a tree. Purpose of the post was to introduce people to what seemed to me to be a fascinating area filled with some valuable trees. Fine if you are not interested in exploration but feel you might get more satisfaction and approval if you stuck to sites devoted to grammar linguistics and English usage

    • This comment has missed the forrest/wood/coppice for the trees.

  • Excellent riposte Jerome!
    I am afraid current research is run by the ‘nitpickers’.
    It will take an ability to dismiss the trivial and take the larger view to make changes in research directions.

  • It’s not just mutations. The key to cancer (or cancers, they’re not all the same even in the same tissue) is not known. Some useful ideas are repressed by orthodoxy but some are only those that we can’t deal with at the mooment especially given the low level of scientific funding and the disproportiobnate investments. In other words, hard as it is to do, we need to keep the perceiption of scandal under control. The estbablishent diabetes world is actively trying to repress known benefit of low-carb diets but the establishment in cancer is not quite so doctrinaire despite the nearly total lack of data supproting alternative ideas.I can’t say that I am an expert on keeping indignation under control but it is necessary.

    • Editorial

      Indignation a good fuel but probably not a good tactic, certainly not in large volumes. Accept that low carb approach to cancer is not actively suppressed but simply side-lined because:
      a) it is old hat – idea dates back over 70 years and was pronounced dead in the 70′s by key cancer opinion leader (don’t have name to hands – Weisman?? – but there is lots of fascinating detail on the history of the idea and how it was kept alive by Pedersen in book out last year “Tripping over the Truth: the metabolic theory of cancer by Travis Christofferson which I’m reading at the moment and plan to do a post on as it seems important.
      b) the low carb diet involves nutrition and my sense is that the cancer establishment view if that cancer is so heavyweight and complicated that something as cranky as eating more avocados and many fewer biscuits couldn’t possibly make a difference.

      Although given the vast sums poured into the genetic approach there is a lot riding on keeping low carbs off the radar.

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