West German Cancer Center, Department of Medical Oncology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Expert Rev Anticancer Ther. 2011 Jul;11(7):1115-30. doi: 10.1586/era.11.61.
Polo-like kinase 1 (Plk1) inhibitors belong to a new class of drugs for the treatment of malignant diseases. They selectively act against a target (Plk1) which is involved in different stages of mitosis such as centrosome maturation, spindle formation, chromosome separation and cytokinesis. Because Plk1 is mainly expressed in proliferating tissues and overexpressed in cancers, its inhibition is potentially less prone to toxicities associated with current antimitotic agents, which also act on nondividing cells. Several Plk1 inhibitors are being evaluated as cancer treatment drugs. Based on the essential role of Plk1 during mitosis, Plk1 inhibitors target all rapidly dividing cells irrespective of their tumor suppressor or oncogene mutations. In this article, their mechanisms of action, efficacy and toxicity profile are discussed.
丝氨酸/苏氨酸激酶 polo 样激酶 1（Plk1）抑制剂属于一种新型的恶性疾病治疗药物。它们选择性地作用于一个靶标（Plk1），该靶标参与有丝分裂的不同阶段，如中心体成熟、纺锤体形成、染色体分离和胞质分裂。由于 Plk1 主要在增殖组织中表达，并在癌症中过度表达，因此其抑制作用不太可能产生与目前抗有丝分裂药物相关的毒性，这些药物也作用于非分裂细胞。几种 Plk1 抑制剂正在被评估为癌症治疗药物。基于 Plk1 在有丝分裂过程中的重要作用，Plk1 抑制剂针对所有快速分裂的细胞，而不管其肿瘤抑制因子或致癌基因突变如何。本文讨论了它们的作用机制、疗效和毒性特征。
