By Jerome Burne
A diagnosis of cancer is really scary. It can seem as if there are only two options, neither very appealing: conventional treatment which promises a lot but is likely to be toxic and gruelling or the complementary route, seen to lack the punch needed to beat cancer. It’s also likely to be dismissed by your authoritative consultant as lacking evidence and only promoted by the peddlers of false hope.
Now there’s a radical new approach to cancer, however, which regards toxic drugs as largely unnecessary and welcomes many non-drug treatments as having a valuable role to play. A few years ago only a few maverick researchers knew about it, lately it’s been getting heavyweight academic attention.
A conference devoted to the metabolic theory of cancer is being held in London tomorrow (Saturday 19th November) by the integrative cancer charity Yes to Life. It is titled: ‘Charging down the wrong path’. Is cancer a metabolic, epigenetic disease? The quote in the title comes from one of the speakers Professor Paul Davies, Principle Investigator at the Centre for the Convergence of Physical Science and Cancer Biology at Arizona State University.
His ‘wrong path’ is the reason why we need a new view of cancer. The mistake has been to think that we can ‘beat cancer’ by focusing on cancer-causing genes. ‘Never has science offered a clearer example of a preoccupation with trees at the expense of the forest,’ he wrote in his book ‘This Idea Must Die’.
The forest in this case is the whole cancer cell and the micro-environment around it.
What are the conditions that favour cancer and which don’t?
Davies is actually an astrophysicist who was asked by the American National Cancer Institute some years ago to look at cancer from the perspective of a physicist, rather than a biologist. ‘They wanted to know if there was something they were missing,’ he says. ‘They were spending five billion-a- year on research yet improvement in treatments was painfully slow.’
I wrote a post on Davies’ work last year which gives background details on his theory on the origins of cancer and the new approach it suggests.
Davies identified the almost exclusive concentration on cancer genes as the ‘wrong path’ and went on to ask such basic questions as why is cancer found all through nature, what are the conditions that favour cancer and what are the ones that make it harder for cancer to thrive? One of the answers involves metabolism – the way cells in a body make energy– because cancer cells make energy in a different, less efficient and more ancient way, than healthy cells do.
‘Healthy cells use oxygen and sugar or glucose which they get from the blood, says Davies. ‘Cancer cells need far less oxygen and a lot more glucose for their energy production.’ And right there you have one way to discourage cancer growth. ‘Expose tumours to hyperbaric oxygen and starve them of sugar by eating a low carbohydrate or even ketogenic diet,’ says Davies.
Looking at the whole cell and its local environment is what many of those non-drug practitioners have been doing for years; the ketogenic diet (getting the body to run on fat-derived energy packets rather than glucose) is widely used and so are diets that keep the system slightly alkaline. Davies identifies an acidic micro-environment as cancer-friendly.
By my age you are riddled with cancer
The metabolic theory doesn’t ignore genes but rather than trying to knock ‘rogue’ ones out, it aims to change their expression – turning them on or off.
‘Cancer is part of us,’ says Davies. ‘By the time you get to my age you are likely to be riddled with cancer cells but a healthy body keeps them in check. They start growing dangerously when the micro-environment becomes more cancer-friendly.’
Shifting this local environment in a more cancer-hostile direction can bring them back under control by changing gene expression. ‘What totally astonished me,’ says Davies ‘was the discovery that among the many things that can affect gene expression are the electrical and physical forces that physicists work with – temperature, electrical polarisation (interferes with the division of fast growing cells), stress and pressure. I leave the question of how to apply them clinically to the next generation.’
So the metabolic theory doesn’t just encourage a non- drug approach, it makes it an obvious part of any effective treatment. This raises the question of just how effective are the pharmaceuticals that now dominate cancer treatment? Are the NCI concerns about effectiveness, which first got Davies involved, still justified?
An article in The BMJ earlier this month gives a ringing yes. Last year the world-wide spend on chemotherapy drugs was £85 billion yet it is clear we are getting a very small bang for this vast outlay of bucks. ‘Chemotherapy drugs have had little effect on survival in adults with metastatic cancer,’ writes Peter Wise, former consultant physician and senior lecturer.
Benefits from chemotherapy – an extra two months
In 200 4 a large study found that: ‘For 90% of patients – including those with the commonest tumours of the lung, prostate colon and breast – drug therapy increased five years survival by less than 2.5% - an overall survival benefit of around three months.’
You might think that the new improved drugs coming on the market would do much better. Not at all. ‘The 48 new drug ‘regimens’ approved by the American FDA between 2002 and 2014,’ writes Wise, ‘had a median overall survival benefit of 2.1 months.’
The piece also makes a detailed critique of the way trials are done. These include using markers for effectiveness, such as shrinking a tumour, which have little connection with the final outcome, and involving patients who are younger and healthier than those who are most likely to be getting the drugs.
Many of the drugs are then released onto the market as fast as possible on the grounds that they are ‘game-changing’ or ‘revolutionary’ which rarely turns out to be the case. Wise concludes: ‘Market driven rather than health driven priorities and practices do not benefit cancer patients.’
Professor Davies also referred to his frustration with market driven practices. ‘The cancer industrial complex demands clinical trial evidence for the metabolic approach but has no interest in funding it because there is no profit in more oxygen and fewer carbohydrates.’
These all seem points worth considering when deciding how much to rely on drugs to treat your cancer.
DNA not the way says genetics pioneer
One of the best accounts of the metabolic theory and its history comes from a book called Tripping Over the Truth: the metabolic theory of cancer by American science writer Travis Christofferson , who is also speaking at the conference. It was published in 2014 and I wrote an enthusiastic review here.
The book traces the metabolic theory back to the ideas of the German Nobel Prize winner Otto Warburg, who first reported that cancer cells made energy in a different way nearly 70 years ago. The finding was then sidelined by the rise of genetics but kept alive by one dogged American researcher. The latest edition of the book has an epilogue that takes the story on and describes some new developments.
For instance, the legendary DNA researchers James Watson, one of the architects of the genetic theory of cancer, recently told the New York Times Magazine that if he were going into cancer research today, he would study biochemistry (cells) rather than molecular biology (genetics).
Among those now accepting the importance of epigenetic changes in triggering and driving cancer is Stanford Medical cancer researcher Parag Mallick, PhD. In August of this year he was quoted as saying that like most other researchers he had been convinced that cancer was the result of genetic mutations in individual cells caused by a carcinogen, such as asbestos or cigarette smoke.
War on cancer needs be replaced with diplomacy
‘But it has turned out that most of the things that cause cancer, including tobacco smoke and asbestos, don’t cause mutations,’ he says. Rather than modifying the genes themselves, smoke and asbestos alter the activity of genes through a collection of processes called epigenetics.’
What this means is that the war on cancer is being replaced by a process of diplomacy. ‘The idea of epigenetic therapy is not to kill the cell,’ says Dr. Jean Pierre Issa of M.D. Anderson. ‘Rather, we are trying to do diplomacy, to change the instructions that have begun running cancer cells. Cancer cells start out as normal cells each of which has the same set of instructions.
‘When a cell becomes cancerous, specific genes that regulate its behavior are turned off by epigenetic changes, which mean the instructions are forgotten. So the aim of epigenetic therapy is to remind the cell that, “Hey, you’re a human cell, you shouldn’t be behaving this way.” And we try to do that by turning the expression of those silenced genes back on and letting them do the work for us.’
And changes in what the drugs are designed to do mean you can use them differently. Promoting epigenetic effects doesn’t need the high toxic doses used in chemotherapy. And the lower doses will make it easier to give drug combinations which are more effective.
Cocktails of drugs with low toxicity
‘Every researcher I’ve spoken with over the last few years believes meaningful results will only come from combinations of treatment’ writes Christofferson. One of these is neuro-oncologist Henry Friedman of Duke University ‘We should be using combination therapies from the get go. Single agent therapies are not likely to be effective in a disease with so many molecular perturbations.”
This is something that is already being tried at the Care Oncology Clinic in London which I’ve written about here. Oncologists at the clinic are using a combination of four, old, off-patent (and so cheap) drugs, never licenced for cancer but known to have anti-cancer effects. Called ‘repurposed’ drugs they are the topic of one of speakers who will be talking about how such drugs made her cancer-free. It so happens that all of the ones being used by the Care Oncology Clinic have an effect on pathways involved in cancer’s energy production system.
Although these new approaches to cancer are exciting, innovative and popular with patients, integrating them into the regulatory system governing cancer treatment it is going to be a challenge, as Christofferson explains.
‘For oncologists, the standard-of-care protocol for the most common cancers is a suit-of-armor. It cuts the chance of being sued for malpractice. But once the cancer has spread patients rarely have long to live and standard-of-care is pretty poor. So what should oncologists do?
‘Give a drug that’s old, very safe and dirt cheap, such as the malaria drug chloroquine, shown to increase survival in brain cancer? But without a clinical trial the FDA won’t approve it so the oncologists could be sued if something goes wrong. But without pharmaceutical funding such trials are almost impossible, leaving oncologists with no incentive to do what could benefit their patients.’
It’s a mark of how much traction the metabolic theory has achieved already that such conundrums are even being considered. Could it eventually create pressure for a medical system driven by health priorities rather than being market driven?