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Erschienen in:

01.03.2007 | Leitthema

Signalübermittlungsinhibitoren

Identifikation und Entwicklung, Tyrosinkinaseinhibitoren, Antiangiogenesefaktoren und Thalidomidanaloga, Proteasomeninhibition

verfasst von: PD Dr. F. Weissinger, D. Fabbro, H. Einsele

Erschienen in: Die Onkologie | Ausgabe 3/2007

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Zusammenfassung

Die Hemmung der Tyrosinkinasen durch intrazellulär wirksame kleine Moleküle ist ein innovatives Therapieprinzip bei der Behandlung maligner Erkrankungen. Imatinib, ein Inhibitor der bcr-abl-Tyrosinkinase, ist Therapiestandard bei der CML und ebenso bei der Behandlung von Phi+-ALL, GIST und der Eosinophilen-Leukämie wirksam. Neue Tyrosinkinaseinhibitoren wie Dasatinib oder Nilotinib können durch andere Bindungseigenschaften bei imatinibresistenter CML Anwendung finden. Multityrosinkinaseinhibitoren wie z. B. Sunitinib und Sorafenib zeigen unter anderem Wirksamkeit beim Nierenzellkarzinom. Durch Erlotinib und Gefitinib ist beim nichtkleinzelligen Bronchialkarzinom eine signifikante Verlängerung des Überlebens möglich. Auch für das metastasierte Pankreaskarzinom zeigt Erlotinib in der Kombination mit Gemcitabin einen Überlebensvorteil. Lapatinib kann in Kombination mit Capecitabin eine Trastuzumab-Resistenz bei HER2-positivem Mammakarzinom überwinden.
Thalidomid und Lenalidomid entfalten ihre Wirkung als immunomodulatorische Medikamente (IMiDs) über verschiedene Mechanismen. Sowohl in der Mono- als auch in der Kombinationstherapie sind sehr gute Remissionsraten und ein verbessertes Gesamtüberleben beim multiplen Myelom erreichbar. Bei Patienten mit einem myelodysplastischen 5q-Syndrom konnte Lenalidomid langfristige Remissionen mit Erreichen einer Transfusionsunabhängigkeit induzieren. Ein komplett neues Therapieprinzip ist die Inhibition des Proteasoms. Die Induktion der Apoptose von Lymphom- und Myelomzelllinien ist auch auf die klinische Anwendung übertragbar und zeigt sehr gute Ansprechraten sowohl in der Mono- als auch in der Kombinationstherapie bei ansonsten refraktärem multiplem Myelom.
Für die beschriebenen neuen Therapieprinzipien, die sog. „targeted therapy“, zeigt sich in der klinischen Anwendung ein Nebenwirkungsspektrum, das sich von den herkömmlicher Zytostatika unterscheidet.
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Metadaten
Titel
Signalübermittlungsinhibitoren
Identifikation und Entwicklung, Tyrosinkinaseinhibitoren, Antiangiogenesefaktoren und Thalidomidanaloga, Proteasomeninhibition
verfasst von
PD Dr. F. Weissinger
D. Fabbro
H. Einsele
Publikationsdatum
01.03.2007
Verlag
Springer-Verlag
Erschienen in
Die Onkologie / Ausgabe 3/2007
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-006-1169-5

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