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

J Mol Med (Berl). 1999 Nov;77(11):792-7. doi: 10.1007/s001099900052.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis
  • Carcinoma, Merkel Cell / drug therapy*
  • Carcinoma, Merkel Cell / metabolism
  • Carcinoma, Merkel Cell / pathology
  • Cell Division / drug effects
  • Farnesol / administration & dosage
  • Farnesol / analogs & derivatives*
  • Farnesol / pharmacology
  • Farnesol / therapeutic use
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, SCID
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Salicylates / administration & dosage
  • Salicylates / pharmacology
  • Salicylates / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Statistics, Nonparametric
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • Antineoplastic Agents
  • Salicylates
  • Tumor Suppressor Protein p53
  • farnesylthiosalicylic acid
  • Farnesol
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)