Cancer Research Campaign: The young survivors

Thirty years ago childhood cancer nearly always resulted in death. Chemotherapy has changed all that. Cherrill Hicks reports

The treatment of childhood cancer is one of the success stories of modern medicine. Nearly two thirds of young sufferers are being cured and researchers are now concentrating their efforts on helping the remaining third - the 500 children who still die of the disease each year.

"There are two misconceptions about children and cancer," says Ross Pinkerton, CRC professor of paediatrics at the Institute of Cancer Research. "Some believe children don't get cancer at all. But about 1,400 children do each year. Others believe it is incurable. It isn't. And I'm optimistic that we'll see a continued improvement in our survival rates."

Childhood cancers are comparatively rare, affecting one in 600 children before the age of 15 - a figure, which has changed little over the past 30 years. However, after accidents and vio- lence, cancer is still the prime cause of death in this age group.

In the vast majority of cases there are no known causes of childhood cancer and no widespread risk factors have been identified. A small proportion - about 5 per cent - are hereditary.

Before the advent of combined chemotherapy, few children survived cancer. Today, advances in treatment and improvements in specialist care have significantly improved survival rates. For some cancers, non-Hodgkin's lymphomas (a cancer of the lymphoid tissue) for example, almost 90 per cent of children recover.

The reason so many childhood cancers are curable by chemotherapy is that they are fundamentally different in type to the adult cancers, says Professor Pinkerton. "Many children have what we call embryonal tumours," he explains. "They resemble undifferentiated foetal tissue and their cells are easier to kill off than adult cancer cells.

"This is why, with adult cancers, specialists tend to use aggressive surgery first, and chemotherapy as an adjunct. But with childhood cancers we use intensive chemotherapy as the primary treatment."

With the dramatic improvement in survival rates, researchers are now monitoring the possible effects of powerful drug treatment years later. "At the [Royal] Marsden [hospital] we have a young adults' clinic for patients in their 20s and 30s who had treatment as children. We are documenting any effects of their treatment on fertility, lung and heart function, growth and hormone production.

"Once we know the long term effects of these drugs, we can try to do something about them," says Professor Pinkerton.

"A Cancer Research Campaign team of researchers have developed, for example, a drug called carboplatin, which is related to platinum but, unlike its forerunners, does not damage the kidneys. And a multi-national study involving several hundred children is currently looking at whether the dosages of powerful drugs for lymphoma can be reduced without affecting cure rates."

One third of child cancer sufferers still die of the disease because, despite drug treatment, some cancers recur. "This is one of the big challenges in children's cancers because the cells are more difficult to kill the second time around," says Professor Pinkerton. "Like adult cancers they mutate to become more resistant to chemotherapy."

A child being treated for leukaemia, for example, may appear to be in remission but may have invisible traces of resistant cancer in the blood and bone marrow. Using molecular technology, doctors are now able to detect this "minimal residual disease" and modify the child's treatment accordingly - with more intensive chemotherapy or a bone marrow transplant.

"It's a bit like dropping a 21b bag of sugar on the kitchen floor," says Tim Eden, CRC professor of paediatric oncology at the University of Manchester. "You may vacuum it up, but for months afterwards you find you're treading on the odd granule. We have to find those granules."

For childhood cancers which still have a poor outlook, researchers are developing promising new treatments - higher doses of powerful drugs can now be given, for example, with the use of autologous stem cell rescue.

Researchers are also looking at how drug resistant cells escape the effects of chemotherapy. "One of the reasons a cancer cell doesn't die is that the drug gets pumped out immediately through the cell membrane. We are now holding clinical trials of drugs to block this pump mechanism so that the drug stays in and the cell `kill' is increased," says Professor Eden.

"At the laboratory level we are trying to identify and target the genetic mechanisms which stop a cancer cell from dying. In the future this may mean knocking out the function of a particular gene or reactivating a gene which is not working properly.

One important issue for the future, he says, is to understand why some cancer cells become resistant to drug therapy. "Then we can work out ways of overcoming this resistance."