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极光激酶抑制剂:癌症中的一类新型靶向药物。

Aurora kinase inhibitors: a new class of targeted drugs in cancer.

作者信息

Gautschi Oliver, Mack Philip C, Davies Angela M, Lara Primo N, Gandara David R

机构信息

University of California Davis Cancer Center, Sacramento, CA 95817, USA.

出版信息

Clin Lung Cancer. 2006 Sep;8(2):93-8. doi: 10.3816/CLC.2006.n.036.

Abstract

Aurora kinases (A, B, and C) are essential for spindle assembly, centrosome maturation, chromosomal segregation, and cytokinesis. Aurora kinases A and B are overexpressed in many cancers, including non-small-cell lung cancer and mesothelioma. Small-molecule inhibitors selective for aurora kinases have shown promising activity in preclinical tumor models. To date, phase I studies with aurora kinase inhibitors have shown that myelosuppression is the dose-limiting toxicity, and disease stabilization was achieved in a number of tumor types, including non-small-cell lung cancer. Phase II trials are under way in selected tumor types. This article reviews the biology of aurora kinases, their potential role in the treatment of lung cancer, and challenges in the clinical development of this unique class of antineoplastic agents.

摘要

极光激酶(A、B和C)对于纺锤体组装、中心体成熟、染色体分离和胞质分裂至关重要。极光激酶A和B在包括非小细胞肺癌和间皮瘤在内的许多癌症中过表达。对极光激酶具有选择性的小分子抑制剂在临床前肿瘤模型中已显示出有前景的活性。迄今为止,极光激酶抑制剂的I期研究表明,骨髓抑制是剂量限制性毒性,并且在包括非小细胞肺癌在内的多种肿瘤类型中实现了疾病稳定。针对特定肿瘤类型的II期试验正在进行中。本文综述了极光激酶的生物学特性、它们在肺癌治疗中的潜在作用以及这类独特抗肿瘤药物临床开发中的挑战。

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