Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice.
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.
Jansen
B
B
Department of Dermatology, University of Vienna, Austria.
Heere-Ress
E
E
Schlagbauer-Wadl
H
H
Halaschek-Wiener
J
J
Waltering
S
S
Moll
I
I
Pehamberger
H
H
Marciano
D
D
Kloog
Y
Y
Wolff
K
K
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
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)