Combining a matrix metalloproteinase inhibitor, a farnesyltransferase inhibitor, and a taxane improves survival in an anaplastic thyroid cancer model.
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.
She
Miaorong
M
Department of General Internal Medicine, Ambulatory Treatment and Emergency Care, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Jim Yeung
Sai-Ching
SC
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008911:Minocycline / Q000008:administration & dosage; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011090:Polyenes / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D014183:Transplantation, Heterologous
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011090:Polyenes; D053284:Polyunsaturated Alkamides; D051231:Farnesyltranstransferase; D008911:Minocycline; C054474:manumycin; D017239:Paclitaxel