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Pharmakogenomik maligner Tumoren

Bedeutung von Zellzyklus- und Apoptosedefekten für Therapieansprechen und Krankheitsprognose

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Zusammenfassung

Nahezu alle nichtchirurgischen Tumortherapien basieren auf dem Prinzip, Zellzyklusarrest oder Zelltod in Tumorzellen auszulösen. Therapieresistenz maligner Tumoren resultiert somit in direkter Konsequenz aus Störungen zentraler Schlüsselgene der Zellzyklus- und Apoptoseregulation. Die Analyse solcher genetischen Veränderungen ermöglicht die Identifikation von Risikopatienten mit ungenügendem Ansprechen auf Chemotherapeutika oder Bestrahlung sowie schlechter Prognose der Tumorerkrankung. Dies ist die Basis für ein molekulares Verständnis der pharmakogenetischen Grundlagen des Ansprechens auf Tumortherapien und auch für den gezielteren klinischen Einsatz von Tumortherapeutika. Insbesondere zeigen aktuelle Daten zur Pharmakogenomik maligner Tumoren, dass Defekte zentraler regulatorischer Gene, z. B. von Komponenten des p53-Signalwegs, nicht immer in globaler Therapieresistenz resultieren, sondern durch Einsatz adäquater Therapiemodalitäten überwunden werden können.

Abstract

Virtually all medical anticancer therapies rely on the induction of cell cycle arrest or cell death in the malignant cells. Consequently, analysis of such genetic events facilitates identification of patients at risk for insufficient response to treatment with chemotherapeutic drugs or ionizing irradiation, and poor survival. Such analyses provide a rational basis for a molecular understanding of the response to anticancer therapies and the clinical use of cancer therapeutics. Notably, recent pharmacogenomic data show that defects in central regulatory genes, e.g., of the p53 pathway, do not result in global resistance to therapy but may be overcome by adequate therapeutic modalities.

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Authors and Affiliations

  1. Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Universitätsklinikum Charité, Campus Berlin-Buch, Humboldt Universität Berlin

    P. T. Daniel, I. Sturm, P. G. Hemmati & D. Güner

  2. Klinische und Molekulare Onkologie, Universitätsklinikum Charité, Campus Berlin-Buch, Humboldt-Universität Berlin, Lindenberger Weg 80, 13125, Berlin-Buch

    P. T. Daniel

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  1. P. T. Daniel
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Correspondence to P. T. Daniel.

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Daniel, P.T., Sturm, I., Hemmati, P.G. et al. Pharmakogenomik maligner Tumoren. Onkologe 10, 46–54 (2004). https://doi.org/10.1007/s00761-003-0628-5

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