文章：

运动蛋白和癌症

Kinesins and cancer

原文发布日期：2012-07-24

DOI: 10.1038/nrc3310

类型: Review Article

开放获取: 否

要点：

1. More than 650 members of the kinesin superfamily have been discovered in eukaryotic organisms. They are categorized into 14 subfamilies on the basis of sequence homology and classified as mitotic kinesins, which are involved in cell division, and non-mitotic kinesins, which are principally involved in intracellular transport.
2. The mitotic spindle is a validated target in cancer chemotherapy, and several agents that target tubulin and that interfere with microtubule dynamics are in clinical use. This success has triggered the search for additional mitotic spindle targets, including mitotic kinases (such as cyclin-dependent kinases, Aurora kinase A, Aurora kinase B and Polo-like kinase 1) and specific mitotic kinesins.
3. EG5 and centromere-associated protein E (CENPE) are two mitotic kinesins that have received much of this attention. Specific inhibitors have been developed and are currently in multiple Phase I or Phase II clinical trials. Other kinesins are also considered potential therapeutic targets and candidate inhibitors have been described.
4. Several non-mitotic kinesins are also involved in tumorigenesis and in the development of resistance to anticancer agents.
5. Several kinesins have multiple functions in mitosis or in intracellular transport. Therefore, careful validation is needed to identify any important side effects and to clarify whether they are viable cancer drug targets.

要点翻译：

1. 在真核生物中已发现超过650个驱动蛋白超家族成员。根据序列同源性，它们被划分为14个亚家族，可分为参与细胞分裂的有丝分裂驱动蛋白和主要参与细胞内运输的非有丝分裂驱动蛋白。
2. 有丝分裂纺锤体是癌症化疗中经过验证的靶点，目前已有多种靶向微管蛋白并干扰微管动力学的药物应用于临床。这一成功引发了对其他有丝分裂纺锤体靶点的探索，包括有丝分裂激酶（如细胞周期蛋白依赖性激酶、极光激酶A、极光激酶B和Polo样激酶1）以及特定的有丝分裂驱动蛋白。
3. EG5着丝粒相关蛋白E（CENPE）是备受关注的两种有丝分裂驱动蛋白。针对它们的特异性抑制剂已被开发出来，目前正在进行多项I期或II期临床试验。其他驱动蛋白也被认为是潜在的治疗靶点，相应的候选抑制剂已有报道。
4. 若干非有丝分裂驱动蛋白也参与肿瘤发生及抗癌药物耐药性的形成。
5. 部分驱动蛋白在有丝分裂或细胞内运输中具有多重功能。因此，需要仔细验证以确定其可能的重要副作用，并明确它们是否可行的癌症药物靶点。

英文摘要：

Kinesins are a family of molecular motors that travel unidirectionally along microtubule tracks to fulfil their many roles in intracellular transport or cell division. Over the past few years kinesins that are involved in mitosis have emerged as potential targets for cancer drug development. Several compounds that inhibit two mitotic kinesins (EG5 (also known as KIF11) and centromere-associated protein E (CENPE)) have entered Phase I and II clinical trials either as monotherapies or in combination with other drugs. Additional mitotic kinesins are currently being validated as drug targets, raising the possibility that the range of kinesin-based drug targets may expand in the future.

摘要翻译： 

驱动蛋白是一类分子马达，它们沿着微管轨道单向移动，以完成细胞内运输或细胞分裂等多种功能。近年来，参与有丝分裂的驱动蛋白已成为癌症药物开发的潜在靶点。一些抑制两种有丝分裂驱动蛋白（EG5（也称为KIF11）和着丝粒相关蛋白E（CENPE））的化合物已进入I期和II期临床试验，无论是作为单药治疗还是与其他药物联合使用。目前，更多的有丝分裂驱动蛋白正在被验证为药物靶点，未来基于驱动蛋白的药物靶点范围可能会扩大。

原文链接：

Kinesins and cancer