Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Utrecht, The Netherlands.
Clin Cancer Res. 2011 Oct 15;17(20):6459-66. doi: 10.1158/1078-0432.CCR-11-0541.
Cytotoxic platinum-doublet chemotherapy that includes antimitotic agents is a current standard of care in advanced non-small cell lung cancer (NSCLC). Microtubule-targeting antimitotics, taxanes, and Vinca alkaloids are effective anticancer therapeutics that affect both dividing and nondividing cells. A new generation of antimitotic agents that target regulatory proteins-mitotic kinases and kinesins-has the potential to overcome the limitations related to the role of tubulin in nondividing cells that are associated with traditional antimitotics. This review concentrates on Polo-like kinase 1, a key regulator of mitosis, outlines a rationale for its development as an anticancer target, and discusses data from preclinical and clinical studies of Plk1 inhibitors with a particular focus on NSCLC.
细胞毒性铂类双联化疗包括抗有丝分裂药物，是晚期非小细胞肺癌（NSCLC）的当前标准治疗方法。微管靶向抗有丝分裂药物、紫杉烷类和长春花生物碱是有效的抗癌治疗药物，它们既影响有丝分裂细胞又影响非有丝分裂细胞。新一代针对调节蛋白——有丝分裂激酶和驱动蛋白的抗有丝分裂药物，有可能克服与传统抗有丝分裂药物相关的非有丝分裂细胞中微管蛋白作用的局限性。本综述集中于 Polo 样激酶 1，即有丝分裂的关键调节因子，概述了将其开发为抗癌靶点的原理，并讨论了 Plk1 抑制剂的临床前和临床研究数据，特别关注 NSCLC。
