Actualité - Innovation

A new therapeutic target for medulloblastomas

Valérie Devillaine
While investigating the scant molecular information available for this type of pediatric cancer, Celio Pouponnot and his colleagues at Institut Curie discovered a therapeutic target for which a potential drug is currently at clinical research stage.
Publication Pouponnot

Medulloblastomas are rare pediatric tumors that affect around a hundred children in France every year, and occur in the cerebellum, a part of the back of the brain. These tumors are categorized into four types, with Group 3 being defined as ‘high-risk’. Standard treatment involves surgery, radiotherapy and chemotherapy, but no targeted treatment is available for these tumors to date. The treatments currently available are only partially effective, and result in significant, long-term adverse effects.

Group 3 medulloblastomas are also the least well characterized. The little information researchers had to work with up until now included the fact that the TGFβ/activin signaling pathway was activated in 5 to 10% of these cancers.

A promising signaling pathway

Celio Pouponnot’s team has been studying medulloblastomas for several years now, and wanted to find out more about the TGFβ/activin signaling pathway: “We were able to demonstrate that this pathway was indeed activated in Group 3 medulloblastomas, and at higher rates than the 5 to 10% we had once thought was the case[CP1] . This activation pathway is a strange one. We know it is generally involved in embryonic development, but in cancer, it plays a double role, sometimes suppressing tumors, and other times having the opposite effect, increasing cancerous cell proliferation and boosting their ability to migrate and form metastases,” explains the researcher.

But the team was also aware that a new drug, galunisertib, is currently being trialed for glioblastoma (a type of brain cancer) in adults, which involves the same activation. The team’s findings are a step forward in potentially trialing this treatment in medulloblastomas, in children for whom traditional treatment has failed to be successful.

Celio Pouponnot plans to continue research into the TGFβ/activin pathway, as it may also play a role in whether or not immune defenses are capable of recognizing and fighting off tumor cells. “But to do this, we need to develop other preclinical case studies,” the researcher adds.

This work was made possible thanks to the integrated approach taken at Institut Curie’s SIREDO center, directed by Olivier Delattre. The SIREDO (Care, Innovation & Research in Childhood, Adolescent & Young-Adult Oncology) is an integrated center that encompasses all these many aspects. This research was conducted as part of a collaborative project with doctors and researchers, pediatric oncology and neurology specialists François Doz and Franck Boudeaut, the latter’s research team, Olivier Ayrault’s research team and international contributions from Michael Taylor and Florence Cavalli (Toronto, Canada).

Further information

An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma


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