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Cancer: the prognosis

August 16, 2006 This article courtesy of Nature News.

Helen Pearson finds out how far we have come, and have to go, to cure cancer.

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When was cancer first recognized?

Cancer has been recognized as a disease for millennia: one of the oldest descriptions comes from an Egyptian papyrus describing breast tumours, and dated to 1500 BC or earlier. By the 1800s it was proposed that cancer was a transformation of normal tissue rather than an invading pathogen. In the eighteenth and nineteenth centuries, hemlock poisoning, swallowing a lizard, or applying ice and salt were some practiced treatments. It wasn't until the Second World War that a drug was finally shown to work albeit modestly against cancer.

How far have we come since then?

We now know that surgery, chemicals and radiation can remove or shrink many cancers, and this remains a mainstay of modern treatment. In the past two decades, major advances in molecular biology and genetics have helped researchers to reveal far more about the molecular changes that occur in cells as they morph from healthy to cancerous ones.

Yet today, the World Health Organisation estimates that the runaway cell division that causes cancer kills more than 7 million people each year, accounting for around 12.5% of all deaths worldwide.

Are there some types of cancer that can now be 'cured'?

A combination of earlier detection, better surgery, radiation, chemotherapy and drugs means that more patients live longer. In the United States, two out of three patients diagnosed with cancer will survive for 5 years after diagnosis, although some cancers can recur many years later. This year, US statistics showed a tiny drop in the absolute number of cancer deaths from 2002 to 2003, despite a growing and aging population. It's the first such decline since records began in 1930.

The prognosis varies radically from one type of cancer to the next. Testicular cancer is one example with very good survival rates: the vast majority of patients go on to live long lives if their cancer is detected early. This is mainly because of a platinum-containing drug called cisplatin, approved for cancer in the 1970s. Cisplatin acts by crosslinking DNA, making it impossible for the cells to duplicate their DNA and thus divide.

Or prevented?

The one thing that could cut cancer rates more than anything else is wiping out tobacco: it is thought to be the cause of at least 30% of cancer deaths in the United States.

Similarly, alcohol, poor diet, lack of exercise and obesity are significant, often unappreciated, contributors to cancer and could account for as much as one-third of cancer deaths, says Carolyn Runowicz at the University of Connecticut Health Center, Farmington, and president of the American Cancer Society. This means that the battle against cancer is actually becoming part of a broader fight against obesity and unhealthy lifestyles. "It's not really what people want to hear," Runowicz says, "they want to know that we can take a pill."

Another strand in prevention is the identification of genetic sequences that predispose people to certain cancers and may allow them to take preventive action. Women carrying certain mutations in the BRCA genes are at high risk of breast and ovarian cancer and can be watched more closely for early signs of disease, or even choose to have a mastectomy to prevent any future disease. But this approach is unlikely to work for all cancer types: for many, an as-yet unknown combination of low-risk genes probably makes people susceptible.

How far do we still have to go?

The survival statistics for certain cancers remain grim because they are often detected late and do not respond well to conventional therapies. In the United States, less than 5% of people with pancreatic cancer and 10% of those with liver cancer survive beyond 5 years after diagnosis. And cancers that have spread to other parts of the body, called metastases, are particularly difficult to treat.

A major part of the problem is that cancer is an enormous collection of different diseases masquerading under one name. There are around 200 different anatomically different cancers and an estimated 250,000 different ones when they are subdivided according to the molecules underlying the disease, says Cancer Research UK's director of clinical programmes Richard Sullivan. In reality, every cancer is subtly different because it arises in a genetically unique individual, by a unique set of changes in their cells. "It's phenomenally complicated," Sullivan says.

What types of new treatments look the most promising?

Researchers are particularly excited by targeted therapies such as the leukaemia drug Gleevec and breast-cancer drug Herceptin, which show that it is possible to identify a protein gone awry and design drugs that specifically act on it. This contrasts with conventional cancer drugs that typically blast all dividing cells indiscriminately and have toxic side effects.

The general aim is to repeat the 'targeted' approach for a host of key proteins now known to be switched on or off inappropriately in subtypes of cancer.

Many researchers are also carrying out more detailed profiles of the genes and proteins that make up certain cancer types. They hope that a particular profile could be used to predict how rapidly a cancer is likely to progress, which drugs will attack it best and whether they are working. "We're just scratching the surface," says cancer biologist Riccardo Dalla-Favera at Columbia University Medical Center in New York.

Will cancer be cured this century?

It is more likely that the death rates will continue to drop slowly rather than cancer vanishing completely. And even then, for some very elderly people, cancer is likely to prove fatal as a part of normal ageing. "You'll never completely eradicate cancer because your body eventually gives up," Sullivan says.

In the meantime, the fight is swallowing enormous amount of money. The National Cancer Institute, one of the biggest spenders, has a budget of US$4.9 billion for 2006 around 17% of the National Institutes of Health total.

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