title: Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice.
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.
authors.affiliation: Department of Dermatology, University of Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Jansen
authors.forename: E
authors.initials: E
authors.lastname: Heere-Ress
authors.forename: H
authors.initials: H
authors.lastname: Schlagbauer-Wadl
authors.forename: J
authors.initials: J
authors.lastname: Halaschek-Wiener
authors.forename: S
authors.initials: S
authors.lastname: Waltering
authors.forename: I
authors.initials: I
authors.lastname: Moll
authors.forename: H
authors.initials: H
authors.lastname: Pehamberger
authors.forename: D
authors.initials: D
authors.lastname: Marciano
authors.forename: Y
authors.initials: Y
authors.lastname: Kloog
authors.forename: K
authors.initials: K
authors.lastname: Wolff
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D015266:Carcinoma, Merkel Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005204:Farnesol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012459:Salicylates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018709:Statistics, Nonparametric; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D012459:Salicylates; D016159:Tumor Suppressor Protein p53; C093323:farnesylthiosalicylic acid; D005204:Farnesol; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)