s-trans-trans-farnesylthiosalicylic-acid and Carcinoma--Merkel-Cell

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.

Topics: Aged; Aged, 80 and over; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Merkel Cell; Cell Division; Farnesol; Female; Humans; Injections, Intraperitoneal; Male; Mice; Mice, SCID; Proto-Oncogene Proteins p21(ras); Salicylates; Skin Neoplasms; Statistics, Nonparametric; Transplantation, Heterologous; Tumor Cells, Cultured; Tumor Suppressor Protein p53