血液恶性肿瘤中的 BCL-2 抑制剂:临床应用和并发症。

IF 6.9 2区 医学 Q1 HEMATOLOGY
Dominic J. Fowler-Shorten , Charlotte Hellmich , Matthew Markham , Kristian M. Bowles , Stuart A. Rushworth
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引用次数: 0

摘要

B细胞淋巴瘤-2(BCL-2)家族蛋白是调节细胞命运的内在凋亡途径的基本调节因子。在许多血液恶性肿瘤中,抗凋亡因子(BCL-2、BCL-XL 和 MCL-1)的过度表达会规避细胞凋亡。为了解决这一癌症特征,人们齐心协力,通过抑制 BCL-2 家族蛋白来诱导细胞凋亡。一系列高选择性 BCL-2 同源 3(BH3)结构域模拟物已用于临床,并正在进行临床试验,用于治疗急性髓性白血病(AML)、慢性髓性白血病(CML)、慢性淋巴细胞白血病(CLL)和多发性骨髓瘤(MM)。这些抑制剂是很有希望的候选药物,既可作为单药,也可用于联合治疗,以改善患者的预后。在滤泡性淋巴瘤等其他疾病中,疗效明显有限。BCL-2家族抑制剂也存在临床问题,包括耐药性、疾病复发、肿瘤溶解综合征和临床相关的细胞减少症。在此,我们对BCL-2抑制的临床益处和相关挑战进行了平衡的分析。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
BCL-2 inhibition in haematological malignancies: Clinical application and complications

B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent apoptosis. To address this cancer hallmark, a concerted effort has been made to induce apoptosis by inhibiting BCL-2 family proteins. A series of highly selective BCL-2 homology 3 (BH3) domain mimetics are in clinical use and in ongoing clinical trials for acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). These inhibitors serve as promising candidates, both as single agents or in combination therapy to improve patient outcomes. In other diseases such as follicular lymphoma, efficacy has been notably limited. There are also clinical problems with BCL-2 family inhibition, including drug resistance, disease relapse, tumour lysis syndrome, and clinically relevant cytopenias. Here, we provide a balanced view on both the clinical benefits of BCL-2 inhibition as well as the associated challenges.

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来源期刊
Blood Reviews
Blood Reviews 医学-血液学
CiteScore
13.80
自引率
1.40%
发文量
78
期刊介绍: Blood Reviews, a highly regarded international journal, serves as a vital information hub, offering comprehensive evaluations of clinical practices and research insights from esteemed experts. Specially commissioned, peer-reviewed articles authored by leading researchers and practitioners ensure extensive global coverage across all sub-specialties of hematology.
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