Pharmakogenomik: Hype oder Hope?

Einleitung

Die Pharmakogenomik gilt heute unter Wissenschaftlern als eine allgemein akzeptierte Forschungsdisziplin und steht darüber hinaus in hohem Maße auch im öffentlichen Interesse. Grund dafür ist ihr propagiertes Konzept einer individualisierten oder personalisierten Medizin, bei der der Anspruch, jedem Patienten eine zielgerichtete und maßgeschneiderte Therapie zukommen zu lassen, im Mittelpunkt steht. Da die klinische Realität heute jedoch noch weit von diesem Ziel entfernt ist [13] [28], besteht bei Klinikern die berechtigte Skepsis, ob und in welchem Umfang die Pharmakogenomik tatsächlich die in sie gesetzten Erwartungen erfüllen kann.

Pharmakogenomik im engeren Sinne versucht, genetische Ursachen für interindividuelle Unterschiede im Therapieansprechen von Arzneimitteln bzw. für unerwünschte Arzneimittelwirkungen (UAW) aufzuklären. Dabei stehen vor allem Gene im Mittelpunkt, die die Pharmakokinetik oder die Pharmakodynamik eines Arzneistoffes betreffen ([Abb. 1]) [25] [26] [41] [67]. Die Pharmakogenomik macht sich dazu die Errungenschaften der Genomforschung der letzten 10 Jahre und ihr Potenzial für eine verbesserte Arzneimitteltherapie zunutze. Diese Entwicklung macht es nunmehr möglich, bisher unbekannte genetische Faktoren für die Pathogenese und die Progression von Erkrankungen (sog. Suszeptibilitätsfaktoren) zu identifizieren und zielgerichtete („targeted”) Therapieoptionen neu zu definieren und somit der Arzneimittelentwicklung innovative Impulse zu geben [16] [68]. Von zentraler Bedeutung ist, dass die nunmehr verfügbar gewordenen, vielversprechenden genomischen Technologien, wie z. B. genomweite Assoziationsstudien (GWA), „deep sequencing” und komplette Exomsequenzierung auch finanziell realisierbar werden. Ebenso fördert der Zugang zu öffentlichen Datenbanken, z. B. „Single Nucleotide Polymorphism database” (dbSNP) [59], „International HapMap Project 1 – 3” [21], 1000-Genom-Projekt [65], „SNPExpress database” [20] sowie „NCI-60 Cancer Cell Line Panel” mit umfangreichen pharmakologischen Daten zu über 100 000 chemischen Verbindungen [61], die schnelle Weiterentwicklung der pharmakogenomischen Forschung.

Abb. 1 Pharmakogenomik und Arzneimitteltherapie. Gene, die die Pharmakokinetik bzw. die Pharmakodynamik eines Arzneimittels beeinflussen, können ursächlich die Wirksamkeit bzw. das Auftreten von unerwünschten Nebenwirkungen beeinflussen.

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