Αρχική World News Genetic discovery could guide treatment for aggressive childhood cancer

Genetic discovery could guide treatment for aggressive childhood cancer

Researcher in a lab

Specific genetic changes in tumours are linked to how aggressive a rare childhood cancer will be, in a finding scientists say could help pave the way for new, tailored treatments.

The genetic changes identified in rhabdomyosarcoma – a type of muscle cancer that mostly affects children – were also linked to the patients’ age when the cancer developed and where it was found in the body. These factors affect how likely a child is to survive their disease.

This work is a fantastic example of how studying the underpinnings of children’s cancers can improve treatment choices.

– Sheona Scales, paediatric clinical trial lead at Cancer Research UK

Findings from this international study – the largest and most comprehensive of the disease to date – could lead to some children being offered more tailored, intensive treatment, while sparing others aggressive interventions.

The study was led by The Institute of Cancer Research (ICR), part-funded by Cancer Research UK, and is published in the Journal of Clinical Oncology.

“Children’s cancers are different to adult cancers. At Cancer Research UK, we are continuing to invest in improving our understanding of children and young people’s cancers to improve outcomes for our youngest cancer patients,” said Sheona Scales, paediatric lead at Cancer Research UK.

A breakthrough study

The international team analysed the DNA from 641 children and young people with rhabdomyosarcoma to look for changes that could be linked to how quickly the cancer grew and how likely it was to respond to treatment, amongst other things.

Researchers looked at the two main sub-types of the disease – fusion-gene positive and fusion-gene negative – separately.

The two main sub-types of rhabdomyosarcoma are fusion-gene positive and fusion gene-negative, depending on whether a so-called ‘fusion gene’ is present. A fusion gene is formed from two previously separate genes, which can affect how the cell functions.

When looking specifically at children with fusion-negative rhabdomyosarcoma, researchers found that tumours with faults in two specific genes – MYOD1 and TP53 – didn’t respond as well to treatment. These faults were also linked to worse survival.

Although the change in the TP53 gene was much rarer in children with fusion-positive rhabdomyosarcoma, it was still linked with worse survival. This has led researchers to classify this genetic fault as a ‘high risk’ indicator in both groups.

Study leader Professor Janet Shipley, Professor of Molecular Pathology at the ICR, said: “By looking at the genetic features of different tumours, we can divide children into different risk groups to help guide their treatment.”

Researchers are now planning to incorporate these new insights into the design of upcoming trials that aim to improve management of the disease.

Learning from the past and looking to the future

As well as uncovering new information, this study has challenged previous findings, including that the presence of a fault in a gene called RAS is linked to poor outcomes.

However, researchers did find that various RAS mutations appeared to be correlated with particular ages of onset for rhabdomyosarcoma. HRAS mutations arose in babies, KRAS mutations in toddlers and NRAS mutations in adolescence.

Data shows that babies have worse survival rates than older children, possibly because doctors avoid using more aggressive treatments like radiation.

Thanks to the findings of this study, researchers now believe that using targeted drugs such as tipifarnib, which blocks HRAS, may be particularly beneficial for young, high-risk patients.

“Children with aggressive and hard to treat cancer often undergo tough treatments that can cause long-term side-effects,” said Scales. “This work will hopefully lead to better outcomes for children with those types of cancers, not just in survival but in the impact their cancer treatment has upon the rest of their lives.”

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