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极光激酶抑制剂:用于妇科恶性肿瘤的潜在分子靶向药物。

Aurora kinase inhibitors: Potential molecular-targeted drugs for gynecologic malignant tumors.

作者信息

Umene Kiyoko, Banno Kouji, Kisu Iori, Yanokura Megumi, Nogami Yuya, Tsuji Kosuke, Masuda Kenta, Ueki Arisa, Kobayashi Yusuke, Yamagami Wataru, Nomura Hiroyuki, Tominaga Eiichiro, Susumu Nobuyuki, Aoki Daisuke

机构信息

Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-8582, Japan.

出版信息

Biomed Rep. 2013 May;1(3):335-340. doi: 10.3892/br.2013.91. Epub 2013 Mar 27.

Abstract

Chemotherapy and surgery are important treatment strategies for gynecologic malignant tumors such as ovarian, cervical and endometrial cancer. However, many anticancer drugs currently available are cytotoxic and cause strong adverse reactions in patients. Aurora kinases have attracted increasing attention in recent years as serine/threonine kinases with various roles in cell division, including chromosomal agglutination and segregation, functions of centromeres, centrosomal maturation, spindle formation and cytokinesis. Aurora kinases are overexpressed in a number of cancers and recent studies have shown that they are involved in onco genesis and cause an aberrant increase in centrosome number, emergence of polykaryocytes and failure of cancer inhibition mechanisms. Thus, drugs that inhibit Aurora kinases are likely to exert anticancer effects in various fields, including the gynecologic field. Aurora kinase inhibitors exert antitumor effects in monotherapy and synergistic effects in combination therapy with taxane-based anticancer agents for gynecologic tumors and are likely to increase the efficacy of existing anticancer drugs. Current Aurora kinase inhibitors include ZM447439, Hesperadin, VX-680/MK-0457, AT9283 and Barasertib, and clinical trials are ongoing to verify the effects of these inhibitors.

摘要

化疗和手术是卵巢癌、宫颈癌和子宫内膜癌等妇科恶性肿瘤的重要治疗策略。然而,目前许多可用的抗癌药物具有细胞毒性,会在患者体内引起强烈的不良反应。近年来,极光激酶作为丝氨酸/苏氨酸激酶受到越来越多的关注,它在细胞分裂中发挥着多种作用,包括染色体凝集和分离、着丝粒功能、中心体成熟、纺锤体形成和胞质分裂。极光激酶在多种癌症中过度表达,最近的研究表明它们参与肿瘤发生,并导致中心体数量异常增加、多核细胞出现以及癌症抑制机制失效。因此,抑制极光激酶的药物可能在包括妇科领域在内的各个领域发挥抗癌作用。极光激酶抑制剂在妇科肿瘤的单药治疗中发挥抗肿瘤作用,在与紫杉烷类抗癌药物联合治疗中发挥协同作用,并且可能提高现有抗癌药物的疗效。目前的极光激酶抑制剂包括ZM447439、海鞘素、VX-680/MK-0457、AT9283和巴瑞替尼,目前正在进行临床试验以验证这些抑制剂的效果。

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