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.