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New approach uncovers tumor promoting signaling pathway in common children’s brain tumor

Press release of KiTZ

A study conducted by researchers of the "Hopp-Children’s Cancer Center at the NCT Heidelberg (KiTZ)" together with colleagues from the Institute Curie (Orsay, France) and the University Hospital Düsseldorf discovered a novel signal transducer promoting medulloblastoma growth. Here, the teams combined two state-of-the-art molecular analysis methods in a project supported by the German Cancer Consortium (DKTK). Their combination approach revealed novel therapeutic targets for a difficult-to-treat brain tumor in children.

The “Hopp Children’s Cancer Center at the NCT Heidelberg” (KiTZ) is a joint initiative of Heidelberg University Hospital and the German Cancer Research Center (DKFZ).

In addition to magnetic resonance imaging (MRI, see photo), molecular genetic analyses play an increasingly important role in the characterization of childhood brain tumors. © Fotolia/Sudok1

Medulloblastoma forms a difficult to treat malignancy, due to its aggressive and fast growth. Using molecular biological analyses, four different subtypes are defined for this disease to date. Especially tumors of the so-called „Group 4“, the most common of these subtypes, are lacking unique druggable markers promoting tumor growth. Combining commonly used genomic analyses with novel proteomic methods – an approach analysing the tumor proteins – the researchers were able to identify a new marker for this medulloblastoma subtype.

The team surrounding Stefan Pfister, KiTZ director, head of the “Pediatric Neurooncology” unit of the DKFZ and senior physician at the Heidelberg University Hospital, together with Olivier Ayrault and his team from the Institute Curie (Orsay, France) and Marc Remke and colleagues of the University Hospital Düsseldorf, were able to describe these new markers. The scientists show the activation of a particular tumor promoting signaling pathway that could not be found with regular genomic analyses approaches.  „We were able to show the connection of a known tumor promoting pathway, the SRC signaling pathway, with the Group 4 medulloblastoma“, says Daisuke Kawauchi, a group leader at the DKFZ department of „pediatric neurooncology“. „This key signaling pathway has not been known so far not know to play a role in these tumors.”

Original publication:
Forget et al. „Aberrant ERBB4-SRC Signaling as a Hallmark of Group 4 Medulloblastoma Revealed by Integrative Phosphoproteomic Profiling”. Cancer Cell 2018. DOI: 10.1016/j.ccell.2018.08.002