Farnesyl transferase inhibitors (FTIs) are a novel class of anti-cancer agents that competitively inhibit farnesyl protein transferase (FPT), and are currently being developed and tested across a wide range of human cancers. Hematologic malignancies, particularly those of myeloid origin, are reasonable disease targets in that they likely overexpress relevant biologic targets, such as Ras, mitogen-activated protein kinase (MAPK), or AKT, that depend upon FPT activity to promote proliferation and survival. Phase I clinical trials using FTIs in acute myelogenous leukemia (AML) and other myeloid malignancies have been performed, demonstrating enzyme target inhibition, low toxicity, and promising response rates. These findings have prompted further development in phase II trials, in order to clarify the response rate and to identify the actual downstream signal transduction targets that may be modified by these agents. It is anticipated that such information will ultimately define the optimal roles of FTIs in patients with AML and other myeloid disorders, facilitate the incorporation of FTIs into current therapeutic strategies for myeloid malignancies, and provide insight into effective methods of combining FTIs with other signal transduction inhibitors.

中文翻译：

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髓样恶性肿瘤中的法呢基转移酶抑制剂。

法呢基转移酶抑制剂（FTI）是一类新型的抗癌药，可竞争性地抑制法呢基蛋白转移酶（FPT），目前正在广泛的人类癌症中进行开发和测试。血液系统恶性肿瘤，尤其是骨髓来源的恶性肿瘤，是合理的疾病靶标，因为它们可能过度表达相关的生物学靶标，例如Ras，丝裂原激活的蛋白激酶（MAPK）或AKT，它们依赖FPT活性来促进增殖和存活。已经进行了在急性骨髓性白血病（AML）和其他髓样恶性肿瘤中使用FTI进行的I期临床试验，证明了酶靶标抑制，低毒性和有希望的应答率。这些发现促进了II期临床试验的进一步发展，为了阐明响应率并确定可能被这些试剂修饰的实际下游信号转导靶标。预计这些信息将最终确定FTI在AML和其他骨髓病患者中的最佳作用，促进将FTI纳入当前针对髓样恶性肿瘤的治疗策略，并提供将FTI与其他信号转导抑制剂结合的有效方法的见解。