Update on aurora kinase inhibitors in gynecologic malignancies.
Update on aurora kinase inhibitors in gynecologic malignancies.
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DOI：
10.2174/157489208786242322
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发表时间：
2008-11
影响因子：
2.8
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Tao X;Chon HS;Fu S;Kavanagh JJ;Hu W
哺乳动物细胞含有三种不同的丝氨酸/苏氨酸蛋白激酶，它们具有高度保守的催化域，包括极光A和B，它们是有丝分裂进入和进展的重要调节因子。极光A和/或B激酶的过度表达与高增殖率和不良预后有关，使其成为抗癌治疗的理想靶点。破坏有丝分裂机制是多种化疗药物所采用的一种行之有效的抗癌策略。许多极光激酶的小分子抑制剂已经被发现，并在体内和体外进行了测试，其中一些目前处于第二阶段测试。这篇综述为读者提供了目前正在研究的每一种极光激酶抑制剂(AKI)的临床前和人体研究的最新结果。这篇论文还详细介绍了为Akis提供的最新数据和第一阶段数据，从而使读者能够比较和对比Akis的个人和与阶级相关的影响。虽然AKI用于抗癌治疗的成功开发和批准仍未解决，但临床前对耐药机制的识别将有助于设计更好的早期临床试验，在这些试验中，可能会在第二阶段测试之前对相关组合进行评估。作者认为，极光激酶是重要的抗癌靶点，与其他与不受控制的肿瘤增殖密切相关的癌基因协同作用，通过提供独特的、靶向的和互补的抗癌机制，扩大可用的抗癌武器。
Mammalian cells contain three distinct serine/threonine protein kinases with highly conserved catalytic domains, including aurora A and B kinases that are essential regulators of mitotic entry and progression. Overexpression of aurora A and/or B kinase is associated with high proliferation rates and poor prognosis, making them ideal targets for anti-cancer therapy. Disruption of mitotic machinery is a proven anti-cancer strategy employed by multiple chemotherapeutic agents. Numerous small molecule inhibitors of the aurora kinases have been discovered and tested in vivo and in vitro, with a few currently in phase II testing. This review provides the reader with updated results from both preclinical and human studies for each of the aurora kinase inhibitors (AKI) that are currently being investigated. The paper also covers in detail the late breaking and phase I data presented for AKIs thereby allowing the reader to compare and contrast individual and class-related effects of AKIs. While the successful development and approval of an AKI for anti-cancer therapy remains unresolved, pre-clinical identification of resistant mechanisms would help design better early phase clinical trials where relevant combinations may be evaluated prior to phase II testing. The authors believe that aurora kinases are important anti-cancer targets that operate in collaboration with other oncogenes intimately involved in uncontrolled tumor proliferation and by providing a unique, targeted and complimentary anti-cancer mechanism, expand the available armamentarium against cancer.
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影响因子：
5.7
作者：
Carpinelli, Patrizia;Ceruti, Roberta;Moll, Jurgen
通讯作者：
Moll, Jurgen
影响因子：
14.9
作者：
Du, J;Hannon, GJ
通讯作者：
Hannon, GJ
DOI：
10.1083/jcb.200208091
发表时间：
2003-04-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ditchfield C;Johnson VL;Tighe A;Ellston R;Haworth C;Johnson T;Mortlock A;Keen N;Taylor SS
通讯作者：
Taylor SS
影响因子：
20.3
作者：
Chng, Wee J.;Braggio, Esteban;Fonseca, Rafael
通讯作者：
Fonseca, Rafael
DOI：
10.1083/jcb.200504097
发表时间：
2005-09-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barros TP;Kinoshita K;Hyman AA;Raff JW
通讯作者：
Raff JW