在急性髓性白血病中,针对eIF4A介导的翻译启动和亡的协同向
Yoke Seng Lee1,2,3, Jonathan D Good1,2,3, Noha Awais1,2,3
1Division of Hematology, Brigham and Women's Hospital, Boston, MA.
Blood neoplasia
|March 12, 2026
概括
准转化启动因子EIF4A1的佐塔提芬,与venetoclax结合,显示出治疗急性髓性白血病 (AML) 的希望. 这种组合协同杀死AML细胞,并在临床前模型中改善存活率.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 由于药物耐药性和复发,急性髓性白血病 (AML) 治疗面临着挑战.
- 针对性治疗,如venetoclax已经改善了选择,但生存率仍然很差.
- 翻译启动因子EIF4A1在AML干细胞/原始细胞中高度表达.
研究的目的:
- 研究EIF4A1作为AML的治疗点.
- 评估单独和与venetoclax结合使用zotatifin抑制eIF4A的疗效.
主要方法:
- 使用zotatifin,抑制真核细胞启动因子4A (eIF4A).
- 核糖体分析和基因组丰富分析以评估翻译效率.
- 在体外和体内研究使用AML细胞系,患者衍生异种移植和组合疗法.
主要成果:
- 佐他提芬降低了细胞循环和瘤信号转录的翻译,降低了AKT,STAT-5和MCL-1的调控.
- 佐塔蒂芬和venetoclax的组合协同杀死AML细胞,并在AML原始细胞中选择性地诱导亡.
- 在临床前AML模型中,组合疗法抑制了瘤负担和延长了生存时间.
结论:
- 通过EIF4A1介导的蛋白转化是AML中可行的治疗标.
- 佐塔蒂芬和venetoclax的组合显示出治疗复发性/耐药性AML的显著潜力.
相关概念视频
Combination Therapies and Personalized Medicine
6.3K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.3K
Targeted Cancer Therapies
9.1K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
9.1K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
61
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
61
The Intrinsic Apoptotic Pathway
9.1K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.1K
The Extrinsic Apoptotic Pathway
9.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.2K


