Targeting apoptosis dysregulation in myeloid malignancies - The promise of a therapeutic revolution

IF 6.9 2区 医学 Q1 HEMATOLOGY
Enrico Santinelli , Maria Rosaria Pascale , Zhuoer Xie , Talha Badar , Maximilian F. Stahl , Jan P. Bewersdorf , Carmelo Gurnari , Amer M. Zeidan
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引用次数: 1

Abstract

In recent years, the therapeutic landscape of myeloid malignancies has been completely revolutionized by the introduction of several new drugs, targeting molecular alterations or pathways crucial for leukemia cells survival. Particularly, many agents targeting apoptosis have been investigated in both pre-clinical and clinical studies. For instance, venetoclax, a pro-apoptotic agent active on BCL-2 signaling, has been successfully used in the treatment of acute myeloid leukemia (AML). The impressive results achieved in this context have made the apoptotic pathway an attractive target also in other myeloid neoplasms, translating the experience of AML. Therefore, several drugs are now under investigation either as single or in combination strategies, due to their synergistic efficacy and capacity to overcome resistance.

In this paper, we will review the mechanisms of apoptosis and the specific drugs currently used and under investigation for the treatment of myeloid neoplasia, identifying critical research necessities for the upcoming years.

靶向髓系恶性肿瘤细胞凋亡失调-治疗革命的希望
近年来,髓系恶性肿瘤的治疗领域已经完全革命性的引入了一些新的药物,靶向分子改变或途径对白血病细胞的生存至关重要。特别是,许多靶向细胞凋亡的药物已经在临床前和临床研究中进行了研究。例如,venetoclax,一种激活BCL-2信号的促凋亡药物,已成功用于治疗急性髓性白血病(AML)。在这种情况下取得的令人印象深刻的结果使得凋亡途径在其他髓系肿瘤中也成为一个有吸引力的靶标,转化了AML的经验。因此,由于几种药物的协同效力和克服耐药性的能力,目前正在对它们单独使用或联合使用的策略进行研究。在本文中,我们将回顾细胞凋亡的机制以及目前用于治疗髓系瘤变的特定药物,并确定未来几年的关键研究需求。
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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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