针对血液系统恶性肿瘤的 MCL-1：原理与进展。
Targeting MCL-1 in hematologic malignancies: Rationale and progress.
机构信息
Alfred Hospital and Monash University, Melbourne, VIC, Australia.
University of Melbourne, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia.
出版信息
Blood Rev. 2020 Nov;44:100672. doi: 10.1016/j.blre.2020.100672. Epub 2020 Feb 21.
Myeloid cell leukemia sequence 1 (MCL-1) is an antiapoptotic protein that plays a key role in promoting cell survival in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL). Overexpression of MCL-1 is associated with treatment resistance and poor prognosis; thus, MCL-1 inhibitors are rational therapeutic options for malignancies depending on MCL-1. Several MCL-1 inhibitors have entered clinical trials, including AZD5991, S64315, AMG 176, and AMG 397. A key area of investigation is whether MCL-1 inhibitors will complement the activity of BCL-2 inhibitors, such as venetoclax, and synergistically enhance anti-tumor efficacy when given in combination with other anti-cancer drugs. Another important question is whether a safe therapeutic window can be found for this new class of inhibitors. In summary, inhibition of MCL-1 shows potential as a treatment for hematologic malignancies and clinical evaluation of MCL-1 inhibitors is currently underway.
髓系细胞白血病序列 1（MCL-1）是一种抗凋亡蛋白，在多发性骨髓瘤（MM）、急性髓系白血病（AML）和非霍奇金淋巴瘤（NHL）中发挥关键作用，促进细胞存活。MCL-1 的过表达与治疗耐药和预后不良相关；因此，MCL-1 抑制剂是依赖 MCL-1 的恶性肿瘤的合理治疗选择。几种 MCL-1 抑制剂已进入临床试验，包括 AZD5991、S64315、AMG 176 和 AMG 397。一个关键的研究领域是 MCL-1 抑制剂是否会补充 BCL-2 抑制剂（如 venetoclax）的活性，以及与其他抗癌药物联合使用时是否会协同增强抗肿瘤疗效。另一个重要问题是是否可以为这一新类抑制剂找到安全的治疗窗。总之，抑制 MCL-1 显示出作为血液恶性肿瘤治疗的潜力，目前正在对 MCL-1 抑制剂进行临床评估。
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