Auf dem Weg zu einer individualisierten Therapie des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) - Stellenwert molekularer Prädiktions- und Prognosefaktoren

Zusammenfassung

Die Therapie des nicht-kleinzelligen Bronchialkarzinoms (NSCLC) erfolgt derzeit stadienadaptiert aufgrund der Erkenntnisse aus klinischen Studien. Das Wissen über spezielle molekulare Veränderungen im Tumor wird (noch) nicht herangezogen, um eine gezielte individuelle Behandlung zu entscheiden. Durch den Einsatz moderner Hochdurchsatz-Verfahren und Analysemöglichkeiten (z. B. Gen-Chip Analysen) erfolgt derzeit in der Onkologie eine exponentielle Zunahme des Wissens über die genetischen Veränderungen in den Zellen und dem Zusammenspiel der Proteine untereinander. Hier kristallisieren sich in jüngster Zeit immer mehr molekulare Faktoren mit prädiktiver (d. h. Vorhersage des Tumoransprechens) und prognostischer (d. h. Vorhersage des Überlebens) Bedeutung beim NSCLC heraus. Zu ihnen zählen unter anderem ERCC1, RRM1 und bestimmte Rezeptor-Tyrosinkinasen. Erste prospektive Studien zeigen bereits, dass die Auswahl der Therapeutika gezielter vorgenommen werden kann, wenn molekulare Marker zuvor aus dem Tumor bestimmt werden. Dieser Übersichtsartikel soll einen Einblick geben, welchen Stellenwert molekulare Marker für die Therapieentscheidung sowohl in der adjuvanten als auch in der palliativen Situation derzeit haben und was in Zukunft möglicherweise in die klinische Praxis übernommen werden wird.

Abstract

The treatment of patients with non-small cell lung carcinoma (NSCLC) is guided by results from clinical studies. Data about molecular changes in the tumour are not used (up to now) to decide for an individualised, tumour-tailored therapy. High-throughput technologies and modern analytical methods (e. g., microarrays) lead to exponentially increasing knowledge about genetic changes in the cells and the interaction of proteins. This results in the discovery of molecular factors with high predictive (prediction of tumour response) and prognostic (prediction of survival) value in NSCLC. Among these are ERCC1, RRM1 and some receptor tyrosine kinases. Preliminary data of prospective studies have shown promising results for the selection of specific drugs, when these tumour markers were analysed. Therefore, this review focuses on the actual value of molecular markers for decision-making in the adjuvant and palliative setting and their probable future introduction into clinical practice.

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