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DOI: 10.1055/s-0029-1224116
© Georg Thieme Verlag KG Stuttgart · New York
Role of the Novel mTOR Inhibitor RAD001 (Everolimus) in Anaplastic Thyroid Cancer
Publikationsverlauf
received 30.03.2009
accepted 28.04.2009
Publikationsdatum:
09. Juni 2009 (online)

Abstract
Activation of the phosphatidylinositol-3-kinase (PI3K) signaling cascade is increasingly recognized as a common feature of thyroid follicular neoplasms. Among the PI3K downstream effectors, the main kinase, directly responsible for the increased cell growth and proliferation, is called mammalian target of rapamycin (mTOR). This central kinase might be directly inhibited via rapamycin and its derivatives. The aim of the present study was to examine whether RAD001 (everolimus) can selectively suppress the proliferation of different anaplastic thyroid cancer (ATC) cells. Five different human ATC cell lines were exposed to different concentrations of RAD001. Importantly, we found a dose-dependent growth inhibition in two ATC cell lines at concentrations of 43.5 and 94.5 nM although not as intensive as within the RAD001 responding K562cell line. The other cell lines revealed a GI50 between 168 to 234 nM. In parallel, quantitative PCR of PCNA displayed a reduced expression of PCNA within the responding cell lines, respectively. In summary, we found a good responding effect in a part of ATC cell lines, which may have a clinical impact.
Key words
anaplastic thyroid carcinoma - RAD001 - everolimus
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Correspondence
C. Papewalis
Endocrine Cancer Center
Department of Endocrinology
Diabetes and Rheumatology
University Hospital Düsseldorf
Moorenstraße5
40225 Düsseldorf
Germany
Telefon: +49/211/810 40 38
Fax: +49/211/811 78 60
eMail: claudia.papewalis@uni-duesseldorf.de