Departments of Leukemia, The University of Texas MD Anderson Cancer Center, 1400 Holcombe Boulevard, Houston, TX, USA.
Blood Cancer J. 2022 Jun 9;12(6):91. doi: 10.1038/s41408-022-00687-5.
Recent advances in FLT3 and IDH targeted inhibition have improved response rates and overall survival in patients with mutations affecting these respective proteins. Despite this success, resistance mechanisms have arisen including mutations that disrupt inhibitor-target interaction, mutations impacting alternate pathways, and changes in the microenvironment. Here we review the role of these proteins in leukemogenesis, their respective inhibitors, mechanisms of resistance, and briefly ongoing studies aimed at overcoming resistance.
最近在 FLT3 和 IDH 靶向抑制方面的进展提高了影响这些相应蛋白的突变患者的反应率和总体生存率。尽管取得了这一成功,但已出现耐药机制,包括破坏抑制剂-靶标相互作用的突变、影响其他途径的突变以及微环境的变化。在这里,我们回顾了这些蛋白在白血病发生中的作用、它们各自的抑制剂、耐药机制以及正在进行的旨在克服耐药性的简要研究。