DNA therapies will change the way cancer is treated – and how tobacco firms sell cigarettes, says Nick Horley.
The management and treatment of cancer is one of the most important – and expensive – duties of the NHS. But did you know that of the £1 billion spent on providing chemotherapy every year, half goes straight down the drain?
The reason is that our medical techniques are essentially based on guesswork. Often, doctors prescribe drugs that have no benefit. They cannot kill the tumour’s cells because they are not targeted at its specific genetic profile.
Yet now the revolution in genetic science offers the chance to have treatments tailored to our personal DNA, and could soon identify those at least and greatest risk of certain diseases, such as smoking-related lung cancer. The consequences are not entirely benign, however; one leading oncologist goes so far as to claim that the tobacco industry could use such techniques to engineer a resurgence in smoking, and that it is just a matter of time before it succeeds in doing so.
The story starts eight years ago, when the 25,000 or so genes in human DNA were first identified by the Human Genome Project. Since then, a large chunk of the scientific community has been racing to work out what each one is for and how it behaves. Every week, press releases announce a new discovery that could transform our health; for example, we can now screen for dangerous mutations of the tumour-suppressing BRAC-2 gene as a matter of routine.
The impact of genetic testing in treating cancer, rather than predicting and preventing it, is growing. For example, breast cancer sufferers who develop early-stage hormone-sensitive cancer – roughly 50 per cent of patients – usually begin their treatment with the surgical removal of their tumour. They then face the dilemma of whether to have chemotherapy as an insurance measure, just in case the cancer spreads. In Britain, about 40 per cent opt for chemo – but very few gain any extra lifespan from it.
But we need not take such a scattergun approach. At the Christie hospital in Manchester, Dr Greg Wilson, a cancer surgeon, now conducts a gene test by the name of Oncotype DX on his patients. Cells collected during their tumour surgery are packed in a paraffin block and sent to a firm called Genomic Health in Redwood City, California, which examines 21 genes known to have a role in cancer survival.
A few days later, Dr Wilson receives the results, a set of graphs indicating how likely that individual’s cancer is to spread, and how likely it is to respond to chemotherapy. “The test allows me to give a much more accurate briefing to the patient,” he says. “Previously, I might have said, 'Chemo will give you five to 10 per cent better chance of being alive in 10 years’, but with Oncotype DX, I can give a more precise figure, for example eight per cent – and that’s not based on statistics from the general population, but on the genes from the patient’s tumour.”
Usually, the Oncotype DX test serves to avert unnecessary chemotherapy for patients whose cancer will not return. Although Genomic Health charges $3,820 (£2,586) per patient, in such cases it pays for itself many times over, sparing the patient needless side-effects, worry and loss of earnings. On the other hand, it is sometimes used to recommend chemotherapy for patients who have incorrectly been given the all-clear – or to identify those who are likely to see their cancer return, but will find that chemotherapy is of no use. For them, hormone therapy and the healing power of their own immune system, which might otherwise have been knocked flat by superfluous toxic drugs, could be the better option.
The buzzword for this approach – which can also help avoid needless chemotherapy for lung, ovarian and colorectal cancer patients – is “personalised medicine”, and according to Professor Karol Sikora, formerly the head of the World Health Organisation’s cancer programme and professor of cancer medicine at Imperial College, “it’s transforming oncology”.
But while a breakthrough this significant is usually trumpeted by the pharmaceutical industry, Oncotype DX has crept on to the medical scene by stealth. Even though Dr Wilson has been using the test for four years, as have many other oncologists around Britain, it has attracted less than 100 words of coverage in national newspapers.
One way to explain this deafening silence is the business model used by the drugs industry. “These predictive tests tell us who not to treat,” says Dr Justin Stebbing, of Imperial College London. “But drug companies have never wanted to narrow the field of patients taking drugs.”
Dr Julian Cole, head of medical affairs at Roche, denies this: “We are committed to identifying which patients will benefit most from which treatments. One example is Herceptin, which is suitable for less than a quarter of all patients with breast cancer.”
Prof Sikora forecasts that, over the next five years, there will be a flood of new gene tests, developed by any of 50 or so specialist diagnostics companies, most of which have no ties to the large pharmaceutical firms. “The result will be that the proportion of patients who are prescribed chemotherapy will halve,” he says. “Drug company bosses know that if their product only works on half the patients and an independent company devises a test for it, their pricing model becomes unsustainable. They’re worried.”
The Association of British Pharmaceutical Industry disagrees. “Better diagnostics leads to better prescribing, which we believe is a good thing,” says a spokesman.
At the moment, the chemotherapy business is set to be worth $64 billion in terms of annual sales by 2017, according to Dr Tom Gray, of the industry watchers Datamonitor. He estimates that of the 24 new drugs in the pipeline, some will be lucrative “blockbusters”, even though they are of “modest efficacy” and carry a price tag of up to £70,000 for one year’s treatment.
However, the Datamonitor numbers do not take into account any of the anticipated new gene tests. Dr Gray concedes that many of the blockbusters “make a great target” for a company such as Genomic Health.
But while such tests may help patients as much as they harm drug firms’ profits, there is another potential winner – the tobacco industry. Prof Sikora says it is just a matter of time before the hundreds of scientists working in that industry identify which genes trigger cancer in smokers. “It’s safe to assume they have been looking for several years,” he says. “It’s the obvious thing to do.”
The self-evident place to start would have been the genes known to metabolise tobacco, but as that has not yet borne fruit, the search will have to be broadened. “They will have to study the entire genome of large groups of people, which could take them five years. But the end result could be a gene-testing kit cheap enough to give as an 18th birthday present, so your children can find out how safe it is for them to start smoking.”
The reason this would make sense for the tobacco companies is that, while the Government likes to tell smokers to quit or die, at least 80 per cent of them do not get lung cancer, and the precise mechanisms that link smoking and cancer are not well understood. Dr Alexandre Akoulitchev, of the diagnostics company Oxford BioDynamics, points out that the Japanese have the longest life expectancy in the world, yet “smoke like chimneys”. Until a few years ago, he says, 50 per cent of Japanese men smoked, but their health services are not overwhelmed by lung cancer. “Their big problem is colorectal cancer, which may have a dietary connection, perhaps with fermented seafood. If they don’t die of colorectal cancer, they live a long life, smoking all the way through.”
Of course, the tobacco industry will never be able to claim outright that smoking could be made safe. Since 1998, when it was forced by a US court to cough up a quarter of a trillion dollars for the treatment of smoking-related diseases, it has been choosing its words carefully. Yet Dr David O’Reilly, the head of public health and scientific affairs at British American Tobacco, still foresees a day when BAT might sell a cigarette no more harmful than going out in the sun.
But will it give the same pleasure? “It’s hard to speculate until we have it in our hands. But history shows consumers will adapt if they’re aware of a reduced risk. Our vision of the future is that they will have a choice of products along a continuum of risk, so those who want to smoke should be allowed to do so.”
In other words, just as we are now seeing personalised drugs tailored to our DNA in order to cure cancer, we can look forward to personalised cigarettes to help us avoid it.
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