CDK4/6信号通路靶向治疗剂在癌症治疗中的研究进展

多数癌症的发生发展都具有细胞周期高度活化的特性。细胞周期蛋白依赖性激酶4/6 (CDK4/6)不仅在细胞有丝分裂中发挥了巨大作用,而且参与了衰老、凋亡和组蛋白调节等诸多生物学过程,并在多种癌症的发生发展中被异常激活。FDA批准了Palbociclib、Ribociclib和Abemaciclib等3种靶向CDK4/6的抑制剂,在临床上也取得了显著的疗效,有效地延长了内分泌治疗耐药的乳腺癌患者以及其他多种类型癌症患者的生存期。但这些抑制剂的临床应用也面临着获得性耐药等问题。文中综述了CDK4/6参与的生物调控过程,及其抑制剂在癌症治疗中的应用和面临的耐药性挑战。

CDK4/6 signaling pathway and its targeted therapeutic agents in cancer therapy: a review

The development and progression of most cancers have been well recognized as the result of highly activated cell cycle. Cyclin dependent kinase 4/6 plays important roles not only in mitosis, but also in multiple biological processes that contribute to cancer development, such as aging, apoptosis and histone modification. Three FDA approved CDK4/6 inhibitors, Palbociclib, Ribociclib and Abemaciclib, have been used as targeted cancer therapeutic agents to benefit patients with endocrine therapy-resistant breast cancer and other types of cancer, prolonging their survival. However, the clinical application of these inhibitors also leads to acquired drug resistance and other problems. This paper reviews the regulatory roles of CDK4/6, the application of CDK4/6 inhibitors in cancer and the challenge of drug resistance.