de Sousa Maria João, Gervaso Lorenzo, Meneses-Medina Monica Isabel, Spada Francesca, Abdel-Rahman Omar, Fazio Nicola
Medical Oncology Department, Instituto Português de Oncologia de Coimbra Francisco Gentil EPE, IPO Coimbra, Coimbra, Portugal.
Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Via Ripamonti 43520141, Milan, Italy.
Curr Oncol Rep. 2022 Jun;24(6):715-722. doi: 10.1007/s11912-022-01251-x. Epub 2022 Mar 9.
Cyclin-dependent kinases (CDKs) are key regulators that play an important role in cell division. Palbociclib, ribociclib and abemaciclib showed significant antitumor activity in several malignancies and, recently, also a myeloprotective effect for trilaciclib when added to chemotherapy. The purpose of this review is to highlight the current evidence for CDK4/6 inhibitors in neuroendocrine neoplasms (NENs).
Preclinical results showed a promising antitumor activity of CDK4/6 inhibitors in neuroendocrine tumors (NETs), but so far, the very few small clinical trials did not show a strong impact on progression free survival (PFS) and objective response in NETs. Meanwhile, the CDK4/6 inhibitor trilaciclib revealed significant effects in reducing chemotherapy-induced myelosuppression in small cell lung cancer (SCLC). Up to date, CDK4/6 inhibitors are still considered investigational in NETs as antitumor agents, whereas trilaciclib can be used in the routine clinical practice in extensive stage SCLC patients for reducing myelotoxicity of standard chemotherapy.
细胞周期蛋白依赖性激酶(CDK)是在细胞分裂中起重要作用的关键调节因子。帕博西尼、瑞博西尼和阿贝西利在多种恶性肿瘤中显示出显著的抗肿瘤活性,最近,三联苯环素与化疗联合使用时对骨髓也有保护作用。本综述的目的是强调CDK4/6抑制剂在神经内分泌肿瘤(NEN)中的现有证据。
临床前结果显示CDK4/6抑制剂在神经内分泌肿瘤(NET)中具有良好的抗肿瘤活性,但到目前为止,极少数小型临床试验并未对NET的无进展生存期(PFS)和客观缓解产生强烈影响。与此同时,CDK4/6抑制剂三联苯环素在降低小细胞肺癌(SCLC)化疗引起的骨髓抑制方面显示出显著效果。迄今为止,CDK4/6抑制剂作为抗肿瘤药物在NET中仍被视为研究性药物,而三联苯环素可用于广泛期SCLC患者的常规临床实践中,以降低标准化疗的骨髓毒性。