Horm Metab Res 2009; 41(10): 752-756
DOI: 10.1055/s-0029-1224116
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Role of the Novel mTOR Inhibitor RAD001 (Everolimus) in Anaplastic Thyroid Cancer

C. Papewalis1 , M. Wuttke 1 , S. Schinner 1 , H. S. Willenberg 1 , A. M. Baran 1 , W. A. Scherbaum 1 , M. Schott 1
  • 1Endocrine Cancer Center, Department of Endocrinology, Diabetes and Rheumatology, University Hospital Düsseldorf, Düsseldorf, Germany
Further Information

Publication History

received 30.03.2009

accepted 28.04.2009

Publication Date:
09 June 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.

References

Correspondence

C. Papewalis

Endocrine Cancer Center

Department of Endocrinology

Diabetes and Rheumatology

University Hospital Düsseldorf

Moorenstraße5

40225 Düsseldorf

Germany

Phone: +49/211/810 40 38

Fax: +49/211/811 78 60

Email: [email protected]