Sarah Boseley and Tim Radford
Cancer is one of the world’s biggest killers. It is a stealthy predator, corrupting the cells of a healthy body, doing damage and hastening death without displaying, for a long while, any outward sign. The treatment is unpleasant and the outcome uncertain.
Nobody can be sure they will not fall prey to some form of the disease. One in three of us will develop it sometime in our lifetime. So when some of the many scientists who spend their lives searching for clues and cures take any sort of step forward, the world goes wild.
So it was with Tamoxifen, the drug researchers in the United States declared prevented breast cancer in high-risk women last month. So it was with p-53, the gene that Scottish scientists say can protect against the toxic chemicals found in tobacco smoke. So it is, most recently, with the news that a combination of two drugs can kill off tumours in mice by blocking their blood supply.
Men and women with terminal cancer wonder if perhaps it is not too late after all. Relatives make the pilgrimage to ask if perhaps their dying mother can have this new treatment. Inevitably, the answer is – not yet.
So are we any nearer to the magic bullet – the cure for cancer that will come in the shape of a pill we can pop with our afternoon tea? In truth, it will probably never be as simple as that, but the chances of our children and grandchild-ren surviving cancer are improving all the time.
Professor Gordon McVie, head of the Cancer Research Campaign in Britain, says the discoveries fall into two groups – those that are of use mainly to other researchers, and those that are of real value to the cancer patient or, more probably, the potential cancer patient.
But the Tamoxifen story, he suggests, is brilliant, because it shows how the two worlds combine. The discovery of a breast cancer susceptibility gene started an argument that raged for three years. You might ask, says McVie, “What’s the point of finding that gene when you have nothing to offer the women who have it?” You have to tell them they have an 80% likelihood of getting cancer in their lifetime and you are terribly sorry.
Enter Tamoxifen. The drug has been in trials in the US, Britain and Italy. The Americans have cut short their study, saying there is incontrovertible evidence that it protects women at high risk from developing the disease. Their scientists say it’s unfair on those women in the trials who’ve been on an inert placebo not to let them to take the real thing. The British still want to know more about the long-term effects.
What about the drugs that kill cancers in mice? Should cancer patients get excited? McVie urges caution. It’s too early to know whether the tumour-busting success of combined angiostatin and endostatin will work in humans. Such translations have failed before.
Nigel Bundred, reader in surgical oncology at the University Hospital of South Manchester, is appalled by the recent spate of splash headlines. It is not scientific breakthroughs that are responsible for the drop in cancer deaths , he says, but improvements in the systems for dealing with them.
Cervical and breast cancer screening have significantly reduced mortality. Improved diagnosis and better access to treatment such as chemotherapy have increased survival. The incidence of cancer is still on the up, but fewer people are dying of it.
Cancer astonishes scientists. It always did. “I wish I had the voice of Homer,” wrote the great biologist JBS Haldane, “to sing of rectal carcinoma.” It fascinated him even as it killed him.
The mortality rate may sound shocking but, looked at another way, cancer is rare. There are 100-million-million cells in the human body, and death from cancer follows because just one of them has gone terminally haywire. Yet all of them go wrong all the time. The DNA in the cell makes 50 000 mistakes an hour, but the miraculous machinery of the human body steps in 50 000 times an hour and sets it right again, and this process goes on hour after hour, decade after decade.
The mystery, says Gerard Evan, is why we die of it at all. Evan is Royal Society professor at University College London, and principal scientist at the Imperial Cancer Research Fund. He has been puzzling over cancer all his working life.
“Cancer is almost so rare it never happens. If we could move the mean incidence of cancer 20 years back in people’s lives, it would cease to be a public health issue.”
Scientists’ goal is to fully understand the natural mechanisms that rein in cancer cells, destroy them, trigger them into committing suicide, or starve them, then they will know where to look for a cure.
Life past reproductive age is a bonus: a consequence of being fit enough to live to 40 to start with. If you make it that far, your cell machinery is good enough to let you carry on, for a while at least. But the problem gets more complicated with time, because cancer is a protean enemy. It is different in different tissues, and even in different individuals. So are the defences.
Different types of tissues will be involved in different types of mutations. However, there are clear, common lessons to be drawn. There will be many common features in rogue cells, even in colon cancer. “You have got to have a mutation that makes you grow uncontrollably,” says Evan. “You have got to have a mutation that makes you live uncontrollably, and you have got to have a mutation that means you cannot be shed properly, in order to be there in the first place.”
So at least three things all have to go wrong before a cancer can start. But some mutations contain their own booby traps.
“There are mutations that make you grow uncontrollably, but those same mutations activate the cell suicide mechanism. In normal cells, that is not a problem,” says Evan. “But tumours are in the wrong place. So a lot of cells that would form tumours, undergo these mutations to make them proliferate, but are in the wrong place to get these survival signals they need. They don’t get them, so they kill themselves off. This cell death programme acts like a booby trap. Unless you know how to stop the booby trap, it will spring. So the very mutation that would cause you to become a tumour now prevents you from becoming one.”
But something does defuse the booby trap: people do die. There may be a one in 100 000-billion chance of two things going wrong simultaneously in a cell – but there are 100-trillion cells: it will happen. So all over the world, scientists are staring at the miracle of programmed cell death, confident that within it lies one answer to cancer. And there are even simpler answers.
Not so long ago cancer researchers relied on the napalm approach: they bombarded the cancer and hoped for the best. The game has changed. Research into the fine machinery of the human system has meant that oncologists can pick up a cancer cell, turn it over, look for its Achilles heel and then develop a drug that – ideally – will defuse its potency.
Evan says he is convinced it will be possible to cure, prevent or stop those cancers that affect younger people. That is not the same as actually eradicating cancer. “One is trying to avoid what one might call premature death – to try to keep people’s quality of life as great as possible until the inevitable point when things fall apart. But cancer is a pretty horrible way to die. So cancer research is not about living for ever. It is about putting off cancer.”
Because there is such intense public interest in cancer – combined with passion and dedication from scientists at the cutting edge of research, the cancer charities’ need to keep up their profile for fund-raising and the drug companies’ need to make a profit – it will be hard to cool the excitement that boils over with every “breakthrough”. People tend not to hear about the setbacks.
For all that, we are slowly progressing. Peter Selby, clinical director of the Imperial Cancer Research Fund, sees the war against cancer in three stages since the 1970s. Chemotherapy brought about cures in most cases of a handful of fairly rare cancers, such as testicular cancer. Then in the Eighties and early Nineties “we made very distinct but small steps forward against common cancers. For breast and bowel cancers we increased cures by about 5%.”
Now we are in the era of biotechnology. It will be a decade before the latest advances turn into widely available treatments. It is hard to remain cool in the battle against cancer. The war against the disease is too fundamentally important for all of us. Only one thing is certain: this is a waiting game.