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Personalisierte Gliomtherapie

Personalized therapy for gliomas

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Zusammenfassung

Aktuell bei Patienten mit Gliomen eingesetzte Therapien beginnen molekulare Faktoren einzubeziehen, sind aber weiterhin wenig individualisiert. Übernommen in die klinische Anwendung und Leitlinien sind bisher in erster Linie genetische und molekulare Marker zur Diagnose bzw. Klassifikation der Gliome und genetische Marker zur Prognoseabschätzung. Die Methylierung des Promoters der O6-Methyl-Guanin-Methyl-Transferase (MGMT) und die Kodeletion von 1p und 19q (1p/19q codel) wurden als Merkmale zur Therapiestratifizierung, d. h. als prädiktive Faktoren, weiterentwickelt und molekulare Marker wie die trunkierte, aber autoaktive Form des Epidermal-growth-factor-Rezeptors (EGFRvIII) und die R132H-Mutation der Isozitratdehydrogenase-1 (IDH-1) in bereits laufenden immuntherapeutischen Studien zur Entwicklung zielgerichteter Therapien eingesetzt. Die Integration funktioneller bildgebender Verfahren in das Therapiemonitoring sowie die Entwicklung standardisierter Bewertungskriterien verbessern zunehmend die Möglichkeiten, bildgebende Biomarker zur Therapiesteuerung einzusetzen. Auswirkungen dieser Entwicklungen sind bereits jetzt in einer spürbar besseren Prognosestratifizierung von Patienten mit Gliomen sowie – bei erhaltener Lebensqualität – in deutlichen Gewinnen an Überlebenszeit in einigen Gliomsubgruppen zu spüren. Bei einer ähnlich dynamischen Weiterentwicklung ist in Kürze eine allgemein akzeptierte deutlich differenziertere Klassifikation der Gliome anhand molekularer Kriterien zu erwarten, die eine rationale personalisierte Therapiesteuerung mit früher Evaluation des Ansprechens deutlich vereinfachen wird.

Summary

Current therapies for patients with malignant gliomas are starting to integrate molecular factors and age. Nonetheless, these therapies are still not sufficiently individualized. Some positive examples of transfer from basic science to clinical application are currently integrated into the standard treatment and guidelines. These are mainly genetic and other molecular factors that improve diagnosis and classification of gliomas and markers supporting prognostication. Examples for predictive biomarkers are methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the codeletion of chromosome arms 1p and 19q (1p/19q codel). The autoactive, truncated form of epidermal growth factor receptor (EGFRvIII) and the R132H mutation of isocitrate dehydrogenase 1 (IDH-1) are used as targets in currently running immunotherapeutic, targeted trials. Integration of functional imaging parameters into the monitoring and development of uniform assessment criteria improve the ability to evaluate therapy response and implement imaging biomarkers to guide therapies. As a result of the current efforts there are better classified prognostic groups and improved survival times with maintained functional and quality of life parameters in some glioma subgroups. Given the current dynamics, an improved, better differentiated classification of brain tumors including molecular parameters as well as more rational precise guiding of therapies with early, uniform response assessment is expected in the near future.

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Einhaltung ethischer Richtlinien

Interessenskonflikt. W. Wick ist in Advisory Boards und als Referent für Roche tätig. Er ist Inhaber von Patenten zur IDH-Immuntherapie und Immunhistochemie und zur molekularen Diagnostik bei APG101. Er ist außerdem Studienleiter der im Text erwähnten Studien: APG101_CD002, GAPVAC und NOA-8. P. Hau ist als Referent für Roche, Medac und TEVA tätig und erhält Beraterhonorare von Roche, Medac und Novocure. Reisekosten wurden von Roche, Medac, TEVA und Novocure übernommen.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Wick, W., Hau, P. Personalisierte Gliomtherapie. Nervenarzt 86, 692–700 (2015). https://doi.org/10.1007/s00115-014-4226-0

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  • DOI: https://doi.org/10.1007/s00115-014-4226-0

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