Scientists believe they may have found a way to treat a rare but devastating cancer that kills young children often within months of their diagnosis.
There is currently no treatment for malignant rhabdoid tumours, which usually develop in the kidneys and have no symptoms in the early stages. By the time they are diagnosed, the cancer has often spread to other organs and is fatal. Most of those affected are infants and toddlers.
The mutated gene that causes the cancer is well known, but scientists have not been able to find a way to target it. However, scientists working for the Institute for Cancer Research (ICR) believe they have a made a breakthrough. They have now identified two other genes that appear to be implicated in driving the growth of the tumour, which produce proteins that can be inhibited by drugs that are already in use in other cancers or are in the development pipeline.
Prof Paul Huang, team leader of the protein networks laboratory at the ICR, says they have found “a chink in the armour” of these very aggressive tumours, using drugs that attack proteins known as kinase inhibitors.
“There are a lot of kinase drugs out there, so we don’t have to re-invent the wheel,” he said. “In many cases in drug discovery you find a new target and spend 10 to 20 years developing drugs against it.”
In this case, they hope that will not be necessary . “We have been able to re-purpose existing drugs, some of which are already approved.”
So far, the drugs have been tested against cancer cells in the laboratory. The scientists, who have published their results in the journal Cell Reports, found that inhibiting proteins produced by one of the genes had little effect, but attacking both of them killed the cancer cells.
The drugs pazopanib, dasatinib and sunitinib were all successful at inhibiting the protein from the PDGFRA gene – but if high levels of protein from the other gene, called FGFR1, remained, the cancer returned and would not respond to treatment even at higher doses. This may explain why, when doctors have tried chemotherapy with their young patients, even where it has worked at first, resistance has quickly set in.
An existing drug called ponatinib, currently in use as treatment for leukaemia, can target both proteins at once. But there are questions over the safety of the drug in children, so there will be a need to screen other drugs to find one with fewer side effects that works.
The cancer is very rare – there is one case in 2 million children – but the work the ICR is doing will pay dividends in other cancers too. About 20% of all cancers have genes from this class.
Studies in mice will now be necessary before the drugs can be tried in children. The ICR is leading the world in the hunt for treatments for very rare children’s cancers, which are very unlikely to make a profit and are not a field that private drug companies are keen to enter.
Prof Paul Workman, chief executive of the ICR in London, said: “We need to see much better, more targeted treatments for children with cancer, that further drive up survival rates and spare children the serious long-term side-effects that conventional chemotherapy can cause.
“This study provides an exciting pointer for how we might treat more effectively an aggressive childhood cancer for which there is currently no cure. It’s crucial, when as here there is a strong scientific rationale for a new treatment approach in children, that we can assess them as rapidly as possible in clinical trials. At the moment, it’s much too easy for pharmaceutical companies to avoid evaluating their drugs in children, even when there is good evidence that they could benefit.”
Jennifer Kelly’s four year-old daughter Grace was diagnosed with malignant rhabdoid tumours two years ago and died soon afterwards. Her mother set up the Grace Kelly Ladybird Trust to fundraise research into childhood cancers.
“Grace went from being a happy, healthy schoolgirl to passing away within three weeks,” said her mother. “She started school in September and didn’t make it to half-term. She was an athlete – she was the monkey hanging upside down from the monkey bars. Even when she was admitted to hospital initially she seemed quite well. It progressed very rapidly.
“It is basically a diagnosis of death, whether they try to hold it at bay with chemotherapy for a while or not. They simply can’t treat them. There is a lack of funding for childhood cancers as a whole. People don’t realise childhood cancer is the biggest medical cause of death in children in the UK. People think it is rare and it actually isn’t. It is that that shocked us more than anything else.”
One in 500 children get some kind of cancer before the age of 14, according to figures from Cancer Research UK. In the UK, 1,700 children under 14 get a diagnosis each year, and 2,300 between the ages of 14 and 20.
Scientists find "chink in armour" of aggressive childhood cancer
