Knudsen Erik S, O'Connor Thomas N, Witkiewicz Agnieszka K
Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Elm and Carlton Street, Buffalo, NY 14263, USA.
Cancer Heterog Plast. 2025;2(3). doi: 10.47248/chp2502030015. Epub 2025 Sep 25.
Progression through the mammalian cell cycle is a highly regulated process to maintain tissue homeostasis. The key regulators of cell cycle transitions are cyclin-dependent kinase (CDK)/Cyclin complexes that phosphorylate substrates such as the RB tumor suppressor to facilitate cellular division. The regulation of G1/S is of particular significance in cancer and is affected by numerous tumor suppressors and oncogenes. Historically, the cell cycle was viewed as a rigidly regulated process, but recent evidence has revealed significant flexibility and differential CDK/Cyclin dependencies across tumor types. These heterogeneous features of cell cycle control have implications for the etiology of different tumor types as well as the response to multiple therapeutic modalities. Most notably, adaptive responses in cell cycle regulatory circuits can contribute to acquired resistance in a variety of contexts, underscoring the importance for tumor biology and disease treatment.
哺乳动物细胞周期的进展是一个高度受调控的过程，以维持组织稳态。细胞周期转换的关键调节因子是细胞周期蛋白依赖性激酶（CDK）/细胞周期蛋白复合物，它们使诸如RB肿瘤抑制因子等底物磷酸化，以促进细胞分裂。G1/S期的调控在癌症中具有特别重要的意义，并且受到众多肿瘤抑制因子和癌基因的影响。从历史上看，细胞周期被视为一个严格调控的过程，但最近的证据表明，不同肿瘤类型在细胞周期蛋白依赖性激酶/细胞周期蛋白依赖性方面具有显著的灵活性和差异。细胞周期控制的这些异质性特征对不同肿瘤类型的病因以及对多种治疗方式的反应都有影响。最值得注意的是，细胞周期调节回路中的适应性反应在多种情况下可导致获得性耐药，这突出了其在肿瘤生物学和疾病治疗中的重要性。
