Prädiktive und prognostische Faktoren in der neoadjuvanten/adjuvanten Therapie gastrointestinaler Tumoren: Wunschdenken oder Realität?

Zusammenfassung

Maligne Tumoren des Gastrointestinaltraktes stellen weltweit eine der Haupttodesursachen durch bösartige Grunderkrankungen dar. Obwohl mit neuartigen Operationstechniken sowie neoadjuvanten/adjuvanten Behandlungskonzepten in den letzten Jahren eine Steigerung der Therapieerfolge erzielt wurde und sich die multimodalen Konzepte zunehmend etablieren, stellen diese Tumorerkrankungen weiterhin eine große Herausforderung dar. Deshalb müssen prädiktive/prognostische Faktoren etabliert werden, die die Erfolgsaussichten der innovativen Behandlungsstrategien optimieren können. Durch moderne molekularbiologische Methoden ist es in den letzten Jahren gelungen, solche „Prädiktionsfaktoren” zu charakterisieren. Dabei wurden Marker aus unterschiedlichen zellulären Prozessen beschrieben: das Tumorsuppressorgen p53, die Zellzyklus-regulierenden Proteine p21 und p27, der Proliferationsmarker Ki-67, der „epidermal growth factor receptor”, HER2/neu, angiogenetische Faktoren („vascular endothelial growth factor”, Cyclooxygenase 2, Thymidin-Phosphorylase), Enzyme involviert in die DNS-Reparaturmechanismen (ERCC1), Enzyme involviert in den 5-Fluorouracil-Stoffwechsel (Thymidylat-Synthase, Dihydropyrimidindehydrogenase) oder andere genetische Phänomene, wie „loss of heterozygosity” oder Mikrosatelliteninstabilität. Die zumeist retrospektiv erzielten Studienergebnisse sind vielversprechend und verlangen nach großen prospektiven Studien, um diese „Prädiktionsmarker” in der Therapie gastrointestinaler Tumoren zu validieren. Danach könnten wir in der Lage sein, vor Beginn eines individuellen multimodalen Behandlungskonzeptes vorauszusagen, ob und wann behandelt werden sollte, sowie mit welcher (neo-)adjuvanten Therapie und in welcher Dosierung der größte Erfolg erzielt werden kann.

Abstract

Malignant gastrointestinal tumors are still worldwide a very common cause of death from cancer. Even though the surgical techniques and the neoadjuvant/adjuvant therapies have improved over the last years and multimodal concepts in cancer treatment have been established, these types of tumors remain a challenge. Therefore predictive/prognostic markers need to be established, to be able to tailor chemotherapies and therefore improve efficacy of neoadjuvant/adjuvant treatment. Over the last years potential predictive/prognostic factors have been characterized by molecularbiological technologies: the tumorsuppressor gene p53, the cell-cycle regulatory proteins p21 and p27, the marker of proliferation Ki-67, the epidermal growth factor receptor, HER2/neu, angiogenetic factors (the vascular endothelial growth factor, cyclooxygenase 2, thymidine phosphorylase), enzymes involved in the DNA-repair-system (ERCC1), enzymes involved in the 5-fluorouracil-metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase) or other genetic alterations, like the loss of heterozygosity or the microsatellite instability. The results of the mainly retrospective studies are promising but prospective studies are needed to validate those markers in the therapy of gastrointestinal tumors. The goal is that we will be able to predict when and with what to treat.

Schlüsselwörter

gastrointestinale Tumoren - (neo-)adjuvante (Radio-)Chemotherapie - prädiktive Faktoren - prognostische Faktoren

Key words

gastrointestinal tumors - (neo-)adjuvant (radio-)chemotherapy - predictive factors - prognostic factors

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