Combining a matrix metalloproteinase inhibitor, a farnesyltransferase inhibitor, and a taxane improves survival in an anaplastic thyroid cancer model

Cancer Lett. 2006 Jul 18;238(2):197-201. doi: 10.1016/j.canlet.2005.07.012. Epub 2005 Sep 8.

Abstract

We previously showed that the in vivo anticancer effects of a combination of manumycin (a farnesyltransferase inhibitor) and paclitaxel (a microtubule inhibitor) against anaplastic thyroid carcinoma (ATC) were partially due to inhibition of angiogenesis. In this study, we investigated the effect of adding minocycline (a matrix metalloproteinase inhibitor) to manumycin and paclitaxel against human ATC cells xenografted in nude mice. The triple-drug combination resulted in the lowest average tumor growth rate, and it conferred significantly better survival than manumycin alone, paclitaxel alone, or manumycin plus paclitaxel. In conclusion, this novel combination deserves further investigation in the treatment of ATC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Enzyme Inhibitors / administration & dosage*
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Humans
  • Matrix Metalloproteinase Inhibitors*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Minocycline / administration & dosage
  • Neoplasm Transplantation
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Polyenes / administration & dosage
  • Polyunsaturated Alkamides
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Transplantation, Heterologous

Substances

  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Polyenes
  • Polyunsaturated Alkamides
  • Farnesyltranstransferase
  • Minocycline
  • manumycin
  • Paclitaxel