慢性粒细胞白血病靶向治疗的分子耐药机制研究进展

Progress in molecular resistance mechanisms of targeted therapy for chronic myeloid leukemia

肿瘤靶向治疗的抵抗或耐药是一个涉及多因素的复杂过程,其最终结果是在治疗压力下具有逃避治疗能力或相对增殖优势的肿瘤克隆被选择性保留。BCR::ABL1融合基因是慢性粒细胞白血病(CML)的主要分子异常,靶向BCR::ABL1融合蛋白的酪氨酸激酶抑制剂(TKI)的开发和应用开创了小分子靶向药物的时代。目前已有多种TKI获批临床应用或在研发中。尽管大多数CML患者对TKI治疗有良好反应,但仍有部分患者原发反应不良或发生耐药复发。随着长期维持治疗的患者和序贯使用多种TKI药物的患者增多,TKI耐药情况也变得更为复杂。文章介绍近年来CML分子耐药机制的研究进展,并分享2021年第63届美国血液学会年会中与之相关的前沿报道。

Resistance or drug-resistant recurrence of targeted tumor therapy is a complex and multi-factorial process,with the final result of tumor clones that can evade treatment or have relative proliferation advantages under treatment pressure being selectively retained.The BCR::ABL1 fusion gene is the primary molecular abnormality of chronic myeloid leukemia(CML),and the development and application of tyrosine kinase inhibitors(TKI)targeting the BCR::ABL1 fusion protein pioneered the era of small molecule targeted therapeutics.Several TKI have been approved for clinical application or in development.Although most CML patients manifest an excellent response to TKI treatment,there are still some patients with poor primary response or relapse with drug resistance.With the increase in the number of patients with long-term maintenance therapy and the sequential use of multiple TKI,the resistance of TKI has become more complicated.This article introduces the research progress of CML molecular resistance mechanisms in recent years and shares the relevant cutting-edge reports at the 63rd American Society of Hematology Annual Meeting in 2021.