Genetic Testing Could Result in Life-Extending Treatment for Incurable Pediatric Brain Tumors

In an article recently published by the Institute of Cancer Research, genetic testing, future clinical trials of immunotherapies, and acquiring the necessary tools needed to personalize treatment for children with incurable brain tumors were discussed.

The article highlighted an international study performed by Professor Chris Jones and a team at The Institute of Cancer Research in London, which included 51 centers in 14 countries. It discovered that genetic testing correlated with potentially life-extending treatment in children with incurable brain tumors.

“This exciting research is giving us the tools to personalise treatment for children with brain cancer,” stated Jones in a recent statement. “It’s vital that we take advantage of advances in research by improving children’s access to genetic testing and clinical trials, so every child has the best possible chance of receiving a drug that may work for them. “The next step is to confirm our findings in a clinical trial where only children with these specific mutations receive Avastin. If that is successful, we can open up a promising new option for paediatric brain cancer by turning an established drug for adult cancers into a targeted treatment for children.”

Additionally, the study showed that while children’s aggressive brain tumors are commonly treated as a single disease, there are, in reality, 10 differential diseases. Consequently, the research indicated genetic testing in children for mutations increases the likelihood they receive the most appropriate treatment. As the positive outcomes of adult cancer patients frequently benefiting from personalized therapies through genetic testing preface as an example, pediatric cancer continues to, surprisingly, trail behind.

However, scientists also assessed the DNA of children taking an adult cancer drug on a clinical trial classified as having ‘failed.” They discovered that a good number of the children with particular genetic traits had responded well to treatment. In fact, some of the children even survived over a year longer than other participants in the trial.

Furthermore, Avastin (bevacizumab) appeared to cause immune cells to flood in to help eliminate their tumors, which indicated that they could be good possibilities for future immunotherapy. Bevacizumab works to block a tumor’s blood supply and direct the immune system to the cancer. The results also revealed that children whose tumors had mutations in the Mitogen-activated protein kinase (MAPK) network of genes benefited from bevacizumab alongside standard treatment.

In a trial that assessed bevacizumab combined with standard treatment of temozolomide and radiotherapy with standard treatment alone in 121 children aged 3 to 18 with high-grade brain tumors, it was found that children did not benefit from bevacizumab. However, upon looking more closely at the genetics of the tumors, it was shown that those whose tumors had mutations in the MAPK network of genes (around 10% to 15% of the total) lived up to 16 months longer than other patients.

Killer T cells (immune cells) were also observed to congregate to tumor sites in many of these children. Since some cases had cancers with more mutations overall, it observed that the immune system picked apart the cancer cells from healthy cells more easily in those cases.

Looking forward, future clinical trials of immunotherapies could involve children with these specific tumors since these trial designs often work best in patients whose cancers have already sparked some immune reaction.

However, it was also noted that children with tumors caused by mutations in the histone H3F3A gene did not benefit from bevacizumab. These subjects had an average survival of merely 7.9 months among having very few immune cells present in and around the tumor.

The study concluded that genetic testing is also likely to assist in directing children with specific mutations towards bevacizumab while steering others away from it in order to provide the most effective treatment.

“We will never see progress in treatment of children’s brain cancers while we continue to lump everyone with these cancers together in one group,” added Jones. “Children deserve better.”

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