Division of Organic and Medicinal Chemistry, Faculty of Chemistry, Wroclaw University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
National Research Council, Institute of Biophysics (IBF-CNR), Milan Unit, Via Corti, 12, 20133 Milan, Italy.
Molecules. 2024 Nov 13;29(22):5334. doi: 10.3390/molecules29225334.
Neoplastic cells are characterized by uncontrolled cell divisions caused by cell cycle dysregulation. Key regulatory proteins governing the transition from the G1 to the S phase are the CDK4 and CDK6 kinases, which are controlled by D-type cyclins. The CDK4/6 kinases enable the use of these proteins as targets for anticancer therapy because they prevent the growth and the development of malignant cells by inhibiting their activity. This paper surveys the clinical trial results concerning palbociclib, the first in-class FDA-approved anticancer drug for hormone-dependent breast cancer. It discusses the therapeutic applications in breast cancer as well as in solid tumors and hematopoietic malignancies. Additionally, the paper presents an analysis of palbociclib resistance acquired during therapy and explores new approaches, such as modifications to palbociclib that enhance its desired activity or open up new therapeutic possibilities (PROTACs).
肿瘤细胞的特征是细胞周期失调导致的不受控制的细胞分裂。调控 G1 期向 S 期过渡的关键调节蛋白是 CDK4 和 CDK6 激酶，它们受 D 型细胞周期蛋白的控制。CDK4/6 激酶可将这些蛋白作为抗癌治疗的靶点，因为它们通过抑制其活性来阻止恶性细胞的生长和发育。本文综述了 palbociclib 的临床试验结果，palbociclib 是首个获得 FDA 批准用于治疗激素依赖性乳腺癌的同类抗癌药物。本文讨论了 palbociclib 在乳腺癌以及实体瘤和血液恶性肿瘤中的治疗应用。此外，本文还分析了在治疗过程中获得的 palbociclib 耐药性，并探讨了新的方法，例如对 palbociclib 进行修饰，以增强其所需的活性或开辟新的治疗可能性（PROTACs）。
