Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice (original) (raw)

Abstract

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor response to a variety of therapeutic strategies. We evaluated the antitumor activity of S-_trans, trans_-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplantation model for human MCC (seven animals per group). FTS injected intraperitoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneously in SCID mice. These effects led to a statistically significant inhibition of MCC growth (P<0.002). The mean tumor weights following FTS or control treatment were 0.32±0.15 g and 1.08±0.29 g, respectively. There was no evidence of FTS related toxicity at the effective dose used. Our findings stress the notion that FTS may qualify as a novel and rational treatment approach for MCC and possibly for other tumors that rely on tyrosine kinase signaling.

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Authors and Affiliations

1. Department of Dermatology, Division of General Dermatology, University of Vienna, Vienna, Austria
   Burkhard Jansen, Elisabeth Heere-Ress, Hermine Schlagbauer-Wadl, Hubert Pehamberger & Klaus Wolff
2. Department of Clinical Pharmacology, Section of Experimental Oncology/Molecular Pharmacology, University of Vienna, Vienna, Austria
   Julius Halaschek-Wiener
3. Department of Dermatology, Mannheim, Germany
   Stephan Waltering
4. Department of Dermatology, University Hospital Eppendorf, Hamburg, Germany
   Ingrid Moll
5. Israel Institute for Biological Research, 70450 Ness Ziona, Israel
   Daniele Marciano
6. Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, 69979 Tel-Aviv, Israel
   Yoel Kloog

Authors

1. Burkhard Jansen
2. Elisabeth Heere-Ress
3. Hermine Schlagbauer-Wadl
4. Julius Halaschek-Wiener
5. Stephan Waltering
6. Ingrid Moll
7. Hubert Pehamberger
8. Daniele Marciano
9. Yoel Kloog
10. Klaus Wolff

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Jansen, B., Heere-Ress, E., Schlagbauer-Wadl, H. et al. Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice.J Mol Med 77, 792–797 (1999). https://doi.org/10.1007/s001099900052

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• Received: 14 June 1999
• Accepted: 31 August 1999
• Published: 06 November 1999
• Issue date: November 1999
• DOI: https://doi.org/10.1007/s001099900052