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A cure for cancer?

Nigel Hawkes

The first vaccine to prevent cancer will soon be in use. Does this mark a turning point in the treatment of the disease?

A dream that has inspired cancer researchers for more than a quarter of a century has come true. The first vaccine to prevent cancer has won a licence and will be in use by the end of the year.

The approval by the US Food and Drug Administration (FDA) of Gardasil, a vaccine to prevent cervical cancer, has reawakened interest in the whole field of cancer vaccines. Gardasil, from Merck, and its rival Cervarix, from GlaxoSmithKline (GSK), will prevent infection by human papilloma virus, which causes cervical cancer. They will save thousands of lives every year.

True, cervical cancer is a special case, as it is known to be caused by a virus. Most cancers are not, so simple vaccines to prevent and treat them are less readily devised. But after years of disappointment, hopes are rising that vaccines against a wide range of cancers may prove effective. Is the tide turning? Some eminent people people think so.

Last week GSK announced results from a trial of its lung cancer vaccine, which produced a one-third reduction in the chances of cancer recurring after surgery, compared with a placebo. Lung cancer is one of the toughest cancers to treat, so these results — though not statistically significant — were “very encouraging”, GSK said. Bigger trials will follow.

Other straws in the wind include good results in tackling prostate and skin cancers, and non-Hodgkin’s lymphoma. If the scale of effort is any guide, cancer researchers and drug companies believe that vaccines can at last make a real contribution. There are more than 100 cancer vaccines in late-stage development from more than 75 companies, and although many will fail, in the next five years about 50 should be launched, analysts believe.

Cancer specialists foresee the day when cancer will be “just another disease”, not the death sentence that it used to be. There will be cures, but most patients are unlikely to be cured completely. For them, it will become a disease that they live with rather than die from.

Already the number of people in this group is growing fast, partly as a result of earlier diagnosis, partly longer survival. But by 2025 this group will be many times larger as cancer vaccines make it possible to blunt the disease’s cutting edge.

Unlike Gardasil and Cervarix, most cancer vaccines are designed not to prevent cancer but to treat it. The reason cancer can spread is that the immune system is often poor at recognising cancer cells as “foreign” and attacking them. Essentially, tumour cells appear normal to it — and even when an attack is launched, cancer cells can develop ways of “hiding”, perhaps by reducing the number of proteins on the cell surface that are normally the targets of antibodies.

The aim of cancer vaccines is to restore or strengthen the immune system’s ability to attack cancer cells. The idea is far from new but for many years made little progress.

“Twenty years ago, people didn’t realise how little they knew about the immunology of cancer,” says Dr Jose Lutzky, of Mount Sinai Medical Centre in Miami Beach. Typically, early results were encouraging but the vaccines failed as soon as large trials were attempted. “The whole field was riddled with high expectations,” says one US researcher. “Then everybody failed.”

Despite this, the idea remains so attractive that research has continued and is growing.Several different methods are being used. The simplest idea is to combine fragments of a cancer cell with an adjuvant — a material known to provoke the immune system into action — in hope that this will create a much stronger immune response.

Another approach is to take specialised white blood cells from the patient, mix them with the cancer cells, then inject them back. Similarly, the idea is that these dendritic cells — the most powerful immune-inducing cells in the body — will help the immune system to recognise and attack the cancer.

Last year the first concrete success for a vaccine using dendritic cells was published. Provenge, made by a Seattle-based company, used dendritic cells taken from prostate cancer patients and engineered them to produce a protein found in about 95 per cent of prostate cancer cells.

The trial showed that 34 per cent of men given Provenge, compared with 11 per cent on a placebo, were alive th

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The manufacturer, the US biotech group Dendreon, hopes to submit data for approval by the FDA later this year.

A different approach is to try to identify proteins that are unique to cancer cells and use them as the basis for a vaccine. One such protein, discovered by Professor Peter Stern at the Paterson Institute for Cancer Research in Manchester, is 5T4, whose normal role is to help the developing embryo to latch on to the mother’s womb.He found that cancer cells reactivate this protein as part of their technique for spreading around the body. Two cancer vaccines have since been made using 5T4. In kidney cancer patients, one trial showed that the vaccine doubled the survival time. And in colorectal cancer a second vaccine using 5T4, made by Oxford BioMedica, provoked a strong immune response and caused tumours to shrink.

Yet another approach exploits a molecule called CTLA-4 that regulates the immune response. By inhibiting CTLA-4 — taking off the immune system’s brakes — scientists at the US National Cancer Institute managed to shrink tumours in patients with malignant melanoma, a form of skin cancer.They used an antibody to block CTLA-4, accompanied by a cancer vaccine designed to promote the immune response. In two out of 14 patients the tumours disappeared entirely, in others they shrank, but some patients showed no benefit.

Such results are enough to keep scientists encouraged, but they are still a long way from practical products. Venture capital companies and Wall Street remain hard to convince, and small companies trying to raise money for cancer vaccine development have had a hard time.

The hope is that growing understanding of cancer will underpin the efforts to create vaccines and produce much better results. The optimists include Professor Stern, who says he is confident that cancer vaccines will be on the market in a few years, to be used alongside traditional cancer drugs.

Professor Louis Weiner, of the Fox Chase Cancer Centre in New York, agrees. “We have a lot of tools now,” he says, “but we have to learn how to use them properly.”

So far it has not really been possible to compare the survival of those given vaccines with survival across the board. The reason is that new cancer treatments are always given to those for whom all other treatments have failed.

Ethically it would not be justified to take a patient off a treatment, even a poor one, to try an unproved vaccine. It is also easier to get marketing approval for products for late-stage disease, though companies can gain a market toehold from which to explore how well the product works in early-stage disease.

A vaccine to knock cancer dead and cure the disease appears unlikely. Much more possible is that, along with drugs, vaccines will prolong survival and help to turn cancer into a chronic disease. People may live for years or even decades with cancer, as HIV-positive people already do.

That, of course, has implications for health budgets, because vaccines will not be cheap and patients will need prolonged support. But compared with the problems of creating a cancer vaccine that actually works, that is a side-issue. Given effective treatments, healthcare systems have usually devised ways of paying for them.

It's too late for my father but perhaps not for me

On a visit home for lunch one Sunday four years ago, I found Dad chopping and cooking vegetables — but instead of charging around the kitchen as usual, he was sitting on a stool. He was hunched-up and his head had retreated into his shoulders. He said that he had a little back pain.

His GP made an appointment for an X-ray, which revealed that one of the neck vertebrae had crumbled and a second was cracking. The hospital couldn’t be sure of the cause but my mother, a doctor, was certain. “The odds are it’s cancer,” she told me in her plain and doctorly way.

My first reaction was to search for a book that we could read and discuss. I found memoirs of celebrities who had battled the disease, self-help guides containing basic information and others that described the science in detail. None seemed to connect.

I started talking to doctors with the idea of writing the book that I could not find. Like many people, I believed that cancer was becoming more prevalent and that medicine had failed to cure it. But as Dad underwent surgery to remove his tumour, I learnt that the past decade has been historic for cancer research and that in a few more decades it will be a disease that we live with rather than die from.

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The paradox of cancer is that it is the wonder of life turned against itself. Just as the fertilised egg becomes two cells, then four, then many until we reach adulthood and consist of a thousand billion cells, so cancer begins as a lone cell that multiplies in a chaotic way until it becomes a cluster, then a lump, then a tumour.

Dad’s illness ebbed and flowed. Eight weeks after his operation he took off his plastic collar and we drank to his good health; three months on, the recovery had stalled. He rallied with radiation therapy but, ten months after his first operation, he woke one morning weak and pale and was rushed to hospital for the last time. In the days and weeks that followed I rearranged the blanket on his legs, helped him into new sets of pyjamas and brought a water bottle to his lips. I realised he had bequeathed to me his wiry, dark hair, the blood vessel that ran across the back of his hands and the squint of his nose. And I wondered if he had also passed on a cancerous predisposition.

In 1982 a series of discoveries transformed our understanding of cancer, which had been thought of as an incredibly complex disease caused by radiation, chemicals and viruses. There is now a much simpler explanation. Genes exist whose malfunction, from any of these causes, could trigger the disease. These genes may not necessarily be inherited, but all cancers have genetic faults at their heart.

Cancer medicine has been haphazard in its progress, but cumulative advances are leading to profound changes. According to Karol Sikora, Professor of Cancer Medicine at Imperial College of Medicine in London, by 2025 cancer will be considered a chronic disease, like diabetes or asthma, that impacts on the way people live but does not lead inexorably to death.

The crude physical diagnostic measures that we use now, such as identification of breast lumps and cervical screening, will be replaced by blood tests and imaging technologies that search for malfunctioning cells long before they become dangerous, so those at risk can be screened. Already, tests for the protein CA125 appear to detect ovarian cancer some 18 months before it would otherwise be diagnosed.

The genetic revolution is also transforming how doctors proceed once a cluster of cells has been detected. In the future cancers will be categorised not by where they are discovered (lung, prostate, breast) but by which genes are causing the malignancy.

Preventative strategies, too, are advancing. Last month the National Institute for Health and Clinical Excellence approved a new class of drugs — aromatase inhibitors such as Herstatin — that discourage the recurrence of breast cancer.

Four years on from Dad’s diagnosis and three years since his death, I am prepared now for the next time that the disease strikes — whether it be in myself, a family member or a friend. I know that this will happen, because one in three of us will develop cancer. Fear and ignorance is no way to deal with it.


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