Division of Hematology, START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain.
Division of Oncology, START Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain.
Oncotarget. 2023 Aug 7;14:749-752. doi: 10.18632/oncotarget.28473.
Most hematological malignancies are characterized by overexpression of certain cancer promoting genes, such as MYC, MCL1 and cyclin D1. Preclinical studies in animal models have shown that CDK9 inhibitors supress the transcription of these anti-apoptotic and pro-survival proteins, and suggest their potential synergism with other drugs. In its first in-human trial, enitociclib demonstrated clinical activity in a small cohort of patients with high grade B lymphoma with MYC and BCL2 and/or BCL6 rearrangements, inducing complete responses in 2 of 7 subjects (29%) in monotherapy. These data suggest CDK9 inhibitors could play a role in the treatment of hematological diseases and could be a great ally when combined with other therapeutic approaches.
大多数血液系统恶性肿瘤的特征是某些致癌基因的过度表达，如 MYC、MCL1 和 cyclin D1。动物模型的临床前研究表明，CDK9 抑制剂可抑制这些抗凋亡和促生存蛋白的转录，并提示其与其他药物具有潜在的协同作用。在首次人体试验中，依尼妥西利在一组具有 MYC 和 BCL2 及/或 BCL6 重排的高级别 B 淋巴瘤的小队列患者中显示出临床活性，在单药治疗中 7 名受试者中的 2 名（29%）诱导完全缓解。这些数据表明 CDK9 抑制剂可能在血液系统疾病的治疗中发挥作用，并且在与其他治疗方法联合使用时可能是一个很好的盟友。
