Hepatozelluläres Karzinom – molekulare Grundlagen und Zielmoleküle für die Therapie

Zusammenfassung

Das hepatozelluläre Karzinom zählt zu den häufigsten Krebserkrankungen weltweit mit einer steigenden Inzidenz in westlichen Ländern. Leberzellkarzinome zeichnen sich durch eine molekulare Vielfalt und ein schlechtes Therapieansprechen aus. Trotz großer Fortschritte in der Diagnostik und Behandlung des Leberzellkarzinoms in den letzten Jahren bleiben die Details der biochemischen Mechanismen weitestgehend unverstanden. Hierdurch wird die Entwicklung neuer Therapiestrategien erheblich erschwert. Die rasante Entwicklung von neuen Verfahren zur Analyse molekularer Mechanismen der Krebsentstehung auf verschiedenen molekularen Ebenen hat wesentlich zum Verständnis der Hepatokarzinogenese beigetragen. So ermöglichen neue Technologien die gleichzeitige Untersuchung tausender molekularer Ziele. Obwohl die Anwendung dieser Ansätze in der klinischen Routine noch begrenzt ist, eröffnen „Next-Generation-Technologien“ bislang ungeahnte Einblicke in die molekularen Veränderungen der Hepatokarzinogenese. Der Einsatz dieser neuen Verfahren birgt ein großes Potenzial, die Diagnostik des hepatozellulären Karzinoms zu verbessern, und neue Ziele für individualisierte Therapien zu identifizieren.

Abstract

Hepatocellular carcinomas rank among the most common cancers worldwide. They are characterized by phenotypic heterogeneity and poor response to treatment modalities. Although considerable progress in diagnosis and management of hepatocellular carcinomas has been made over the last decade, the exact biology of liver cancer remains poorly understood, overall hindering the development of new therapeutic strategies. The development of whole-genome analyses on different molecular levels greatly advanced our understanding of hepatocarcinogenesis by simultaneously investigating thousands of molecular targets. Although implementation of the results from these analyses in routine clinical practice is still limited, these next generation technologies offer unprecedented insights into the molecular mechanisms of the development of liver cancer. Overall, great promise rests on whole genomic approaches to improve the diagnostic testing and to identify novel targets for individualized treatment modalities in liver cancer.

Schlüsselwörter

Lebertumor - hepatozelluläres Karzinom - molekulare Pathogenese - Genexpressionprofile - Zielmoleküle der Therapie

Keywords

liver cancer - hepatocellular carcinoma - molecular pathogenesis - gene expression profile - targeted therapy

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