Brunner Thomas B, Hahn Stephen M, Gupta Anjali K, Muschel Ruth J, McKenna W Gillies, Bernhard Eric J
Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104-6072, USA.
Cancer Res. 2003 Sep 15;63(18):5656-68.
This article presents an overview of preclinical studies and clinical trials of a number of independently derived farnesyltransferase inhibitors (FTIs). Potential targets and biological modes of action of FTIs are discussed, and the results of clinical trials are summarized. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in clinical Phase II-III trials. These results reveal a substantial gap in the understanding of the complex activity of FTIs and their interactions with cytotoxic agents. We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs.
本文概述了多种独立衍生的法尼基转移酶抑制剂（FTIs）的临床前研究和临床试验。讨论了FTIs的潜在靶点和生物学作用模式，并总结了临床试验结果。FTIs在临床前研究中作为单一药物或联合用药具有显著疗效，这与II-III期临床试验中的中等效果形成对比。这些结果揭示了在理解FTIs的复杂活性及其与细胞毒性药物的相互作用方面存在很大差距。我们得出结论，考虑到各药物的生物学活性，将FTIs与其他疗法合理联合使用，可能会改善FTIs的临床疗效。
