A new look at treatments for childhood cancers
Children rarely develop tumours, but if they do, the prognosis is uncertain. Sometimes, the growth just disappears, without therapy. Unfortunately, few families are so lucky, and there are only a handful of specifically developed treatments. The EU-funded ASSET project is finding better ways to tackle some of the cancers that can appear in early life.
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Medulloblastoma and neuroblastoma are tumours that mainly affect small children; Ewing sarcoma is a disease that peaks in the teenage years. At the moment, it is hard to tell how such tumours, once diagnosed, are likely to progress, and how best to treat them.
ASSET set out to address this challenge. Three years into the project, the team has already proposed new combinations of existing drugs that are expected to treat specific childhood cancers more effectively and produce fewer side effects.
These advances may reach clinics in as little as two years. Admittedly, this may seem like a very long time for patients facing cancer today. But it is considerably faster than the development of new drugs, where the lead times can exceed a decade.
Speed, says project coordinator Professor Walter Kolch of University College Dublin, is one of the team’s priorities, which is why the researchers are determined to refine the use of existing drugs. But, of course, ASSET is also exploring options for new treatments. It is doing so through an in-depth investigation of the molecular mechanisms that cause tumours.
To identify these mechanisms, the partners are using a systems biology approach. “Instead of analysing single molecules,” says Kolch, “the systems biology approach analyses how molecules interact with each other and with other processes. So it’s not so much about what’s wrong with a single molecule, but more about how what’s wrong with a single molecule impacts on a wide network of molecules in the cell.”
To explain, he uses the metaphor of an orchestra: a symphony is a collective effort. If a single instrument plays out of tune, cacophony could ensue.
ASSET is establishing how many discordant instruments it takes for this to happen. Or rather, how many genetic mutations are needed to cause a tumour.
“The mutations that occur in tumours mainly impinge on so-called signal construction networks, the regulatory networks which control what the cell does: whether a cell grows, whether it dies, whether it differentiates,” Kolch explains. If there is something wrong in this communication, the cell ends up following a different beat.
That said, he adds, the human system is fairly robust and, depending on their nature or extent, mutations don’t necessarily spell trouble. As we age, we acquire an increasing number of them, and it is much harder to work out which ones are actually related to disease.
Hence the emphasis on childhood tumours, where the key mutations can be more readily observed than in tumours that are more likely to develop in later life. “Colorectal cancers can have up to 1 000 or more mutations,” says Kolch. “Medulloblastomas on average have around 10.”
All together now
The partners involved in ASSET combine expertise that covers the whole process, from fundamental research to clinical application. This complementarity, says Kolch, is crucial. “Our work,” he adds, “shows how computational modelling can help to elucidate the causes of diseases and guide the development of new therapies.”
The implications of the team’s work extend well beyond its remit. ASSET is also looking into the similarities of the molecular miscommunication causing childhood cancers and a number of other tumours, such as melanomas.
In doing so, the project is helping to consolidate a new understanding of tumours that approaches them as resulting from disruptions in cellular communication. This new approach could pave the way to more effective therapies across the board.
4th February 2014 - World Cancer Day