Professor David Walker is a paediatric oncologist and works at the University of Nottingham and in Queen’s Medical Centre Hospital in Nottingham. He has sat on our Scientific Advisory Panel to assess applications to our research funding rounds and explains ‘Why children’s cancers need their own research’.
Cancer is many, many thousands of diseases, not just one. The tissues in children, for example their bones, lungs, kidneys etc. are all growing and multiplying. Sometimes a mutation occurs in a child’s genes that means those cells multiply in a cancerous way rather than a normal way. Children’s cancers are a product of their growth and development and that makes them different to adult cancers, because adult cancers are a product of getting older.
The most common cancer that happens in childhood is acute lymphatic leukaemia (ALL). It’s a cancer of the immune system. In the first five years of your life you’re building an immune library to defend you against infections for the rest of your life. The leukaemia gene is in the part of the mechanism that designs new antibodies. But while it’s making new antibodies, every so often it goes wrong and produces a leukaemia instead of making a new antibody.
The second most common group is brain tumours. Brain tumours account for about a quarter of all children’s cancers. In the first six years of life the brain is growing massively. As the brain grows there are different mechanisms involved in that brain growth and those mechanisms can go wrong and generate a tumour as that tissue is growing.
I started working in this field about 30 years ago. When I started about half of the children with leukaemia were cured but half of them sadly died despite the therapy offered at the time. Now in ALL over 80-90 per cent of the children are cured, in some subtypes almost 100 per cent are cured. There are, however, leukaemias that aren’t easily curable and you have to give strong treatment to try and win. We don’t cure all children, but we cure many more than we used to.
The sort of treatments we’re using are still based upon chemotherapy drugs. One of the things that has made childhood cancer treatment successful is that children are very resilient. They can tolerate a much bigger dose per body weight than an adult can so we’re able to give bigger doses that are more effective. Also, the tumour types are less diverse. Generally they only have one or two genetic mutations and so they respond all at once rather than having subgroups that can take over.
The side-effects of chemotherapy affect children as much as adults. The side effects can make them sick, make their hair fall out and make them lose weight. Their blood counts can be affected and they need treatment for infections and complications of the bone marrow being turned off by the treatment for a while. They almost always recover due to the technical skills of our medical and nursing staff who look after the children after each course of treatment. Sometimes we use very big doses of drugs which are life-threatening in their nature.
Children’s cancers need their own research because they’re different. Although they have names that say they’re a cancer, the vast majority of them are unique to childhood.
Over the last 30 years of my career we’ve collected a lot of information about how well we do things. It’s very easy to take measurements of how many people are alive, so survival rates are very powerful drivers for change.
Therefore, where there have been poor survival rates we’ve focused our efforts on trying to investigate new drug combinations, doing trials, testing new things – always using survival rates as our driver for change. That’s really been very, very successful. But that’s driven an intensification of the drug therapy we use, we’re now at the boundaries of tolerance.
So the next driver for change is how to do better with less toxicity and that’s where the research comes in. If we can find drugs that work well without lots of side-effects, then the next phase will be to make the drug treatment less burdensome for the child – and the family.
To make better treatments with less toxicity we’ve got to work more cleverly. An enormous amount of research over the last 20 years has gone towards understanding the genetic mutations that are driving the cancers in children. If we understand the mutations that are driving the cancer, then we can design drugs that target those mutations, with the hope that they will turn the cancer off.
This is what we call precision medicine. It’s finding a target, finding a drug that hits that target and then giving it to people. The problem is that there are a lot of mutations – a lot of targets and we don’t have a bunch of new drugs to hit those targets. So we’re looking for new drugs that will hit those mutations and that are safe to use in children.
There lies the challenge in research now and for the future.
Professor David Walker BMedSci, BM, BS, FRCP, FRCPCH
David Walker speaks about why children need their own cancer research.