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Herausforderungen in der Diagnose und Behandlung von Rezidivgliomen

Neue Substanzen und Möglichkeiten des therapeutischen Einsatzes von Stammzellen

Challenges in Diagnosis and Treatment of Recurrent Glioma. Novel Compounds and Therapeutic Use of Stem Cells

  • THERAPIE
  • GRAND ROUNDS
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Zusammenfassung

Trotz ermutigender Daten in der Primärtherapie von Glioblastompatienten mit Methylierung des Promotors der O6-Methylguanyl-Methyltransferase (MGMT) ist neben der weiteren Optimierung dieser Therapie vor allem die Entwicklung von effektiven Rezidivtherapien vordringlich. In Analogie zu präklinischen Ergebnissen wurde vermutet, dass das Verständnis molekularer prognostischer und insbesondere für eine spezifische Therapie prädiktiver Parameter eine verbesserte Patientenselektion vor Therapie- oder Studienbeginn ermögliche und damit den unselektiven Einsatz selektiv wirkender Therapien verhindere. Aktuell verfügbare molekulare Parameter sind allerdings vor allem prognostisch und nicht prädiktiv. Aktuelle multinationale Studienkonzepte bei malignen Gliomen schließen dennoch erstmals Patienten nach vorhergehender molekularer Untersuchung des 1p/19q-Status oder der Methylierung des MGMT-Promotors ein. Eine Herausforderung für neue Studien ist neben der unmittelbaren Verbesserung der Therapie die Etablierung molekularer prädiktiver Signaturen. Aufgrund der drängenden klinischen Situation und der biologischen Spezifika von hirneigenen Tumoren werden aktuell auch neuartige Konzepte wie die Entwicklung zellulärer Vehikel für die Therapie oder die Verwendung von lentiviral tranduziertem, alkylanzienresistentem Knochenmark untersucht.

Abstract

Classic chemo- or radiotherapy alone are not going to make significant impact in the future treatment of malignant glioma. A better understanding of molecular prognostic or preferentially predictive molecular markers enables an improved patient selection prior to radio- or chemotherapy and reduces the risk of unselective administration of targeted therapies. Over the past years, loss of heterozygosity on chromosomes 1p/19q in anaplastic oligodendro - glial tumors as well as analysis of promoter methylation of the O6-methylguanine-DNA methyltransferase harbored important prognostic and the latter even predictive information on the sensitivity toward an alkylating chemotherapy. Newly developed multinational studies on malignant glioma for the first time ever include patients according to molecular parameters. Novel molecular signatures as well as targeted therapeutics ask for new studies, preferentially in combination with cytotoxic chemotherapeutics or radiotherapy.

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Authors and Affiliations

  1. Klinische Kooperationseinheit Neuroonkologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    Markus Weiler, Lorna Whyte, Sibylle Hodecker &  Wolfgang Wick

  2. Abteilung Neuroonkologie, Universitätsklinikum Heidelberg, Heidelberg, Germany

    Markus Weiler &  Wolfgang Wick

  3. Abteilung Neuroonkologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Wolfgang Wick

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  1. Markus Weiler
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  4. Wolfgang Wick
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Correspondence to Wolfgang Wick.

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Weiler, M., Whyte, L., Hodecker, S. et al. Herausforderungen in der Diagnose und Behandlung von Rezidivgliomen. Onkopipeline 2, 23–29 (2009). https://doi.org/10.1007/s15035-009-0143-2

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