Tumor-selektive Apoptose-Induktion durch TRAIL: Ein neuer therapeutischer „Weg” in der Onkologie?

Zusammenfassung

Fragestellung: Die physiologische Bedeutung des TNF (Tumornekrosefaktor)-related apoptosis-inducing ligand (TRAIL) in der Apoptose soll dargestellt und sein möglicher Einsatz in der uro-onkologischen Therapie diskutiert werden.Material und Methodik: Die Übersichtsarbeit präsentiert und diskutiert die Literatur zur Identifizierung von TRAIL und seinen Rezeptoren sowie zu seiner onkologischen Bedeutung.Ergebnisse: Große Fortschritte in der Apoptose-Forschung sind jüngst durch die Identifizierung und Charakterisierung von TRAIL als ein neues Mitglied der TNF-Superfamilie erzielt worden. Basierend auf den in vitro gewonnenen Erkenntnissen der letzten drei bis vier Jahren ist 1999 zum erstenmal über die erfolgreiche Anwendung von TRAIL in vivo berichtet worden. Die systemische Applikation von TRAIL in SCID Mäusen führte zur Tumorrückbildung bis hin zur kompletten Remission von subkutanen Mamma- und Kolonkarzinomen. Zahlreiche Arbeitsgruppen untersuchen derzeit Nieren- und Prostatakarzinom-Zelllinien auf ihre TRAIL-Sensitivität hin. Jüngste In-vitro-Studien hinsichtlich einer TRAIL-induzierten gesteigerten Chemosensibilität von Tumorzellen zeigen eine signifikant erhöhte Apoptose-Rate durch die Kombination von TRAIL mit unterschiedlichen Chemotherapeutika.Schlussfolgerung: Die Ergänzung von Chemo- oder Radiotherapieregimen durch TRAIL sowie die Kombination von TRAIL mit gen- und immuntherapeutischen Strategien kann zukünftig vielversprechende Perspektiven für die onkologische Therapie von Tumorerkrankungen eröffnen.

Abstract

Purpose: The physiological significance of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in apoptosis is presented herein. Its potential application as a therapeutic agent in urologic oncology is discussed.Materials and Methods: The pertinent literature on the molecular biology of TRAIL, its receptors and future potential for therapy in urologic oncology is reviewed and duscussed.Results: The recent discovery and characterization of TRAIL has led to further insight into the apoptotic process. Based on preceding in vitro studies, the first in vivo study using TRAIL was conducted and published in 1999. Systemic application of TRAIL in SCID mice resulted in tumor regression of subcutaneously implanted mammary and colon cancer. Several groups are loking into TRAIL sensitivity to prostate and renal cancer cellines. Recent in vitro data showed a significant increase of apoptotic cell death rate following the combined application of TRAIL and chemotherapeutics.Conclusions: In the future, TRAIL may be used in combination with other immunotherapies or gene therapies providing a synergistic effect or enhancing the efficacy of chemotherapeutic or radiotherapeutic regimens.

Key words:

Apoptosis - Tumor necrosis factor - Receptors tumor necrosis factor - Membrane glycoproteins - Signal transduction

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