Der Onkologe

, 17:670

Pathophysiologie und Molekulardiagnostik beim nichtkleinzelligen Lungenkarzinom

Leitthema
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Zusammenfassung

Lungenkarzinome sind die häufigste tumorbedingte Todesursache in westlichen Industrienationen trotz kontinuierlicher Verbesserung der diagnostischen und therapeutischen Ansätze [1]. Vielversprechend ist die Entwicklung von zielgerichteten Substanzen („targeted drugs“) gegen onkogene Pathomechanismen des Bronchialkarzinoms („non-small cell lung cancer“, NSCLC). So kommen inzwischen Therapien zum Einsatz, die gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) sowie gegen das transformierende EML4-ALK-Fusionsprotein („echinoderm microtubule-associated protein-like 4 gene“ und „anaplastic lymphoma kinase“) gerichtet sind. Diese Ansätze kommen jedoch fast nur Patienten zugute, die nie geraucht haben und relativ seltene Subtypen von Adenokarzinomen aufweisen. Gerichtete therapeutische Optionen für die häufigen Plattenepithelkarzinome bei Rauchern gibt es bisher noch nicht. Kürzlich jedoch wurden Amplifikationen des Fibroblastenwachstumsfaktorrezeptor-Typ-1(FGFR1)-Gens als mögliche therapeutische Zielstruktur in dieser Patientengruppe identifiziert und finden gerade den Weg in erste klinische Studien. Der folgende Beitrag gibt eine Übersicht über die Pathomechanismen und die Molekulardiagnostik des Lungenkarzinoms zur Therapiestratifizierung.

Schlüsselwörter

Lungenkarzinom EGFR-Gene FGFR1-Tyrosinkinase Humanes EML4-ALK-Fusionsprotein Proteinkinaseinhibitor 

Pathophysiology and molecular diagnostics in non-small cell lung cancer

Abstract

Lung cancer is the most common tumor-related cause of death in western industrialized countries, despite continuous improvement in both diagnostic and therapeutic approaches. However, the development of targeted drugs against the critical oncogenic mechanisms in lung cancer is promising. Compounds targeting epidermal growth factor receptors (EGFR) and EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and anaplastic lymphoma kinase) fusion protein are already in use. However, predominantly patients with adenocarcinomas of the lung who have never smoked gain benefit from these developments. Targeted therapies for the more frequent squamous cell carcinomas often found in smokers have been lacking. Recently, the amplification of the fibroblast growth factor receptor type 1 (FGFR1) gene was identified as a possible target in this patient group and is currently finding its way into clinical trials. The underlying pathology and molecular diagnostics necessary to successfully stratify patients for the novel, targeted therapies in lung cancer are discussed.

Keywords

Lung cancer EGFR genes FGFR1 tyrosine kinase Human EML4-ALK fusion protein Protein kinase inhibitor 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Institut für Pathologie der Universität zu KölnKölnDeutschland

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