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Z Gastroenterol 2008; 46(12): 1384-1392
DOI: 10.1055/s-2008-1027655
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Molekulare Mechanismen und klinische Auswirkungen der Tumorkachexie

Molecular Mechanisms and its Clinical Impact in Cancer CachexiaJ. Bachmann1 , H. Friess1 , M. E. Martignoni1
  • 1Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar
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Publikationsverlauf

Manuskript eingetroffen: 27.1.2008

Manuskript akzeptiert: 27.6.2008

Publikationsdatum:
03. Dezember 2008 (online)

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Zusammenfassung

Kachexie beschreibt einen „schlechten Zustand” eines Patienten; dieses Syndrom kann bei chronischen benignen Erkrankungen (wie Morbus Crohn, Herzinsuffizienz, chronischen Nierenerkrankungen) sowie malignen Erkrankungen auftreten und stellt einen wesentlichen prognostischen Faktor dar. Anhand der vorliegenden Publikation soll der aktuelle Stand der Forschung zu pathophysiologischen Mechanismen der Kachexie insbesondere beim Pankreaskarzinom dargelegt werden. Der Gewichtsverlust bei malignen Erkrankungen ist vor allem auf Anorexie mit daraus resultierender Mangelernährung und einen progredienten Abbau von Muskel- und Fettgewebe zurückzuführen. An dieser Entwicklung sind verschiedene Zytokine beteiligt (u. a. TNF-α, IFN-γ, IL-1, IL-6). Über den Ubiquitin-Proteasom-Signalweg wird der wesentliche Anteil des Proteins abgebaut, in diesen greift auch der Proteolysis inducing Factor (PIF) ein; der Nachweis erhöhter Mengen einer hormonabhängigen Lipase bei kachektischen Tumorpatienten weist darauf hin, dass ein gesteigerter Fettkatabolismus für den Verlust von Fettgewebe wichtig zu sein scheint. Die Entwicklung einer effektiven pharmakologischen Therapie stellt die zentrale klinische Herausforderung dar; bisher konnte keine einen lang anhaltenden Effekt auf das Überleben bei Patienten mit einer Tumorkachexie erbringen. Kachexie ist eine schwerwiegende Erkrankung, die besonders häufig bei Patienten mit Pankreaskarzinom auftritt. Die Kachexie beeinträchtigt nachhaltig die Lebensqualität und verschlechtert wesentlich die Prognose. Ziel der Forschung muss sein, in zentrale Stellen der Kachexie-Regelkreise einzugreifen.

Abstract

Cachexia is a term used to describe the poor status of a patient suffering from a benign disease (Crohn’s disease, chronic heart and kidney failure) as well as from a malignant disease. Cachexia has an important impact on the survival and morbidity in patients with cancer. The aim of this study is to elucidate the pathophysiology in cancer cachexia with a special emphasis on pancreatic cancer. The dramatic weight loss in malignant diseases is due to anorexia resulting in malnutrition and is characterised by a progressive loss of muscle and fat tissue. Different cytokines like TNF-α, IFN-γ, IL-1, IL-6 are involved in this process. Via the ubiquitin-proteasome pathway, in which also the proteolysis inducing factor (PIF) is involved, the majority of protein is degraded. In patients with cancer cachexia we find an elevated level of lipases, which indicates that rather fat catabolism and not reduced fat synthesis is the main factor in fat metabolism. The development of an effective (pharmacological) treatment is still the main challenge. As yet, none of the used therapies show a long-lasting effect on weight stabilisation and survial. Cachexia is an important issue, especially in pancreatic cancer; it influences the qualitiy of life and has an important impact on survival. Today, there are only a few different pharmacological therapies used in the treatment of cancer cachexia, but each and every single treatment has failed to show a persistent effect on survival. The aim of research and treatment is to interrupt the natural clinical course of cachexia.

Schlüsselwörter

Kachexie - Survival - Pankreaskarzinom - Gewichtsverlust

Key words

cachexia - survival - pancreatic cancer - loss of weight

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PD Dr. M. E. Martignoni

Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München

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