Farnesylthiosalicylic acid inhibits the growth of human Merkel cell carcinoma in SCID mice

Merkel cell carcinoma (MCC) is a neuroendocrine malignancy showing poor res ponse to a variety of therapeutic strategies. We evaluated the antitumor ac tivity of S-trans, trans-farnesylthiosalicylic acid (FTS), a new inhibitor of Ras signal transduction, in a newly established SCID mouse xenotransplan tation model for human MCC (seven animals per group). FTS injected intraper itoneally at 5 mg/kg per day for 2 weeks up-regulated the tumor suppressor p53 and induced tumor cell apoptosis in established MCCs growing subcutaneo usly in SCID mice. These effects led to a statistically significant inhibit ion of MCC growth (P < 0.002). The mean tumor weights following FTS or cont rol 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 fi ndings stress the notion that FTS may qualify as a novel and rational treat ment approach for MCC and possibly for other tumors that rely on tyrosine k inase signaling.