Acute leukemia is a common malignancy among children and adults worldwide and many patients suffer from chronic health issues using current therapeutic approaches. Therefore, there is a great need for the development of novel and more specific therapies with fewer side effects. The family of Polo-like kinases (Plks) is a group of five serine/threonine kinases that play an important role in cell cycle regulation and are critical targets for therapeutic invention. Plk1 and Plk4 are novel targets for cancer therapy as leukemic cells often express higher levels than normal cells. In contrast, Plk2 and Plk3 are considered to be tumor suppressors. Several small molecule inhibitors have been developed for targeting Plk1 inhibition. Despite reaching phase III clinical trials, one of the ATP-competitive Plk1 inhibitor, volasertib, did not induce an objective clinical response and even caused lethal side effects in some patients. In order to improve the specificity of the Plk1 inhibitors and reduce off-target side effects, novel RNA interference (RNAi)-based therapies have been developed. In this review, we summarize the mechanisms of action of the Plk family members in acute leukemia, describe preclinical studies and clinical trials involving Plk-targeting drugs and discuss novel approaches in Plk targeting.

中文翻译：

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Polo 样激酶和急性白血病。


急性白血病是全世界儿童和成人中的常见恶性肿瘤，许多患者在使用当前的治疗方法时患有慢性健康问题。因此，非常需要开发新的、更特异且副作用更少的疗法。 Polo 样激酶 (Plks) 家族是一组五种丝氨酸/苏氨酸激酶，它们在细胞周期调节中发挥重要作用，并且是治疗发明的关键靶点。 Plk1 和 Plk4 是癌症治疗的新靶点，因为白血病细胞的表达水平通常高于正常细胞。相反，Plk2 和 Plk3 被认为是肿瘤抑制因子。几种小分子抑制剂已被开发用于靶向 Plk1 抑制。尽管已达到 III 期临床试验，但 ATP 竞争性 Plk1 抑制剂之一 volasertib 并未引起客观的临床反应，甚至在一些患者中引起致命的副作用。为了提高 Plk1 抑制剂的特异性并减少脱靶副作用，人们开发了基于 RNA 干扰 (RNAi) 的新型疗法。在这篇综述中，我们总结了 Plk 家族成员在急性白血病中的作用机制，描述了涉及 Plk 靶向药物的临床前研究和临床试验，并讨论了 Plk 靶向的新方法。