University of São Paulo: Study unravels mechanism of rare pediatric brain cancer and points path to treatment

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A study conducted by researchers from Brazil, Australia, Austria and the United States has advanced the understanding of a type of pediatric cancer without pharmacological treatment options and with a low survival rate. The results, published in the journal Neuro-Oncology , pave the way for the search for more specific therapies.


“The so-called ependymomas are very heterogeneous central nervous system tumors and without many treatment options besides surgery and radiotherapy. Our study focused on the so-called supratentorial ependymoma with fusion between the C11orf95 and RELA genes [ST-RELA] , a frequent subgroup in the pediatric population, aggressive, with a poor prognosis and without specific treatment”, explains Taciani de Almeida Magalhães , first author of the study, carried out during her doctorate at the Faculty of Medicine of Ribeirão Preto (FMRP) at USP with support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp).

The work is part of a Thematic Project coordinated by Luiz Gonzaga Tone , professor at FMRP, who supervised the doctoral research and is one of the co-authors of the article.

This type of ependymoma mainly affects children aged around 8 years (at the time of diagnosis). The five-year survival rate after treatment is approximately 30%, particularly in patients in whom total removal of the tumor through surgery is not possible.


Early diagnosis means greater chances of curing childhood cancer
There are no specific drugs and, therefore, the only therapeutic option available, in addition to surgery, is radiotherapy, which can cause serious cognitive and motor sequelae in children.

The researchers discovered, with the help of different techniques, that in this tumor the so-called Hedgehog (Hh) cell signaling pathway is highly activated. Therefore, in the laboratory, they treated tumors with Sonidegib – a drug that inhibits the Hh pathway and is currently in clinical trials for other types of cancer that affect the central nervous system.

When evaluating the treated tumors, however, the researchers observed that they lost certain structures known as primary cilia and, as a result, became resistant to the drug. It was necessary to bring the eyelashes back.

Back on the bench, the group found that cilia formation was regulated by a specific protein, AURKA. Not by chance present in other tumors, the protein also had a specific inhibitor in clinical trials, Alisertib.

In addition to Sonidegib, the researchers then started to treat the tumors with Alisertib. The primary cilia were not lost and Sonidegib was able to act, successfully promoting the death of tumor cells, without affecting healthy ones.

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