Sbarro Institute for Cancer Research and Molecular Medicine, Department of Biology, Temple University, 1900 N. 12th St., Room 431, Philadelphia, PA, 19122-6017, USA.
Medical Oncology Unit, Clinical Cancer Centre, IRCCS-Arcispedale S. Maria Nuova, Reggio Emilia, Italy.
J Exp Clin Cancer Res. 2018 Feb 23;37(1):36. doi: 10.1186/s13046-018-0704-8.
Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety.
目前对急性髓细胞白血病(AML)的治疗效果并不理想,但对疾病病理生物学和基因组学的深入了解,已促使人们对新型靶向治疗和合理联合治疗进行临床研究。靶向 AML 中失调的细胞周期蛋白依赖性激酶 9(CDK9)途径是一种很有吸引力的方法。抑制 CDK9 会导致受超级增强子调控的细胞存活基因(如 MCL-1、MYC 和细胞周期蛋白 D1)下调。由于 CDK9 抑制剂是非选择性的,因此目前正在使用预测性生物标志物来帮助识别最有可能对 CDK9 抑制剂产生反应的患者,以期提高疗效和安全性。