Der Weg in die personalisierte Therapie von gastrointestinalen Tumorerkrankungen – Möglichkeiten und Limitationen

Zusammenfassung

Es ist das Ziel einer palliativen Chemotherapie die Überlebensrate zu verbessern und gleichzeitig ein Maximum an Lebensqualität für die Betroffenen zu erhalten. Während wir einerseits noch immer die optimale Nutzung traditioneller Chemotherapeutika untersuchen, hat andererseits die Einführung zielgerichteter Therapien die therapeutischen Möglichkeiten bedeutend erweitert. Interessanterweise konnten aktuelle klinische Studien die zugrunde gelegten molekularen Konzepte nicht immer bestätigen. Neuere Daten weisen darauf hin, dass nicht Veränderungen in einzelnen Genen oder Signalwegen, sondern Veränderungen in Signaltransduktionsnetzwerken für die Entstehung und Propagation der meisten Tumore verantwortlich sind. Dies bedeutet, dass ein effektives therapeutisches Konzept pathophysiologisch relevante Signalnetze treffen muss und sich nicht darauf beschränken kann, nur einzelne Proteine zu inhibieren. Zweck dieser Übersichtsarbeit ist es aktuelle Konzepte und Probleme der Tumortherapie an beispielhaften Ergebnissen von klinischen Studien (limitiert auf Pankreaskarzinom und Kolonkarzinom) darzustellen und die derzeitige Interpretation dieser Ergebnisse zu diskutieren.

Abstract

The aim of palliative chemotherapy is to increase survival whilst maintaining optimal quality of life for the individual patient. While the best use of traditional chemotherapeutical agents continues to be explored, the introduction of targeted therapies has significantly broadened the therapeutic options. Yet it is interesting to note that the results of current trials did not always confirm the underlying molecular concepts. Recent data have suggested that altered pathways underlie the development of cancer, not just altered genes. Thus an effective therapeutic agent will have to target pathophysiologically relevant signalling networks, rather than individual proteins. This review presents current concepts and problems of cancer treatment, highlighting results from recent clinical trials of colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying mechanisms.

Kolonkarzinom - Pankreaskarzinom - Signaltransduktion - targeted therapy

colorectal cancer - pancreatic cancer - signal transduction - targeted personalized treatment

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