Department of Pathology and Laboratory Medicine, 1300 York Avenue, C316, New York, NY 10065, USA.
Department of Pathology and Laboratory Medicine, Program in Immunology and Microbial Pathogenesis, Weill Cornell Medical College, 1300 York Avenue, Room C316, New York, NY 10065, USA.
Hematol Oncol Clin North Am. 2020 Oct;34(5):809-823. doi: 10.1016/j.hoc.2020.05.003. Epub 2020 Aug 1.
Cell cycle dysregulation caused by aberrant cyclin D1 and CDK4 expression is a major determinant for proliferation of cancer cells in mantle cell lymphoma (MCL). Inhibition of CDK4/6 induces G1 arrest of MCL cells in patients, appearing to deepen and prolong the clinical response to partner agents. This article reviews aberrations of cell cycle genes in MCL cells and clinical trials of CDK4/6 inhibitors for MCL. Integrative longitudinal functional genomics is discussed as a strategy to discover genomic drivers for resistance in cancer cells and cancer-immune interactions that potentially contribute to the clinical response to palbociclib combination therapy in MCL.
细胞周期失调是套细胞淋巴瘤（MCL）中癌细胞增殖的主要决定因素，其由异常 cyclin D1 和 CDK4 表达引起。CDK4/6 抑制剂可诱导 MCL 患者细胞 G1 期阻滞，似乎加深和延长了对联合用药的临床反应。本文综述了 MCL 细胞中细胞周期基因的异常以及 CDK4/6 抑制剂治疗 MCL 的临床试验。还讨论了整合的纵向功能基因组学策略，以发现癌细胞耐药的基因组驱动因素以及可能有助于 MCL 患者对帕博西利联合治疗产生临床反应的癌-免疫相互作用。
