PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma.
PI3 kinase/AKT pathway as a therapeutic target in multiple myeloma.
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DOI：
10.2217/14796694.3.6.639
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发表时间：
2007-12-01
期刊：
影响因子：
--
通讯作者：
Lonial, Sagar
中科院分区：
文献类型：
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作者：
Harvey, R Donald;Lonial, Sagar
多发性骨髓瘤新疗法的发展依赖于对导致细胞增殖和存活的事件的全面了解。控制调节生长信号的通路是治疗骨髓瘤的一种新兴的补充方法。PI3K/Akt通路是重要的细胞功能的中央守门人，包括黏附、血管生成、迁移和耐药性的产生。已建立的蛋白质和基因如mTOR、P53、NF-kappaB和Bad都通过PI3K和Akt的激活来调节，使它们成为具有广泛下游作用的有吸引力的靶点。直接抑制PI3K已经在细胞系和动物模型中显示出令人印象深刻的肿瘤抑制和消退，包括SF1126在内的多种药物目前正在进行临床试验。针对Akt的药物，如Perifosine，也在开发中。这些药物与现有疗法的结合是改善骨髓瘤治疗的合理途径。
The development of novel therapies for multiple myeloma depends on a comprehensive understanding of the events leading to cellular proliferation and survival. Controlling pathways that regulate growth signals is an emerging and complementary approach to myeloma treatment. The PI3K/Akt pathway is a central gatekeeper for crucial cellular functions including adhesion, angiogenesis, migration and development of drug resistance. Established proteins and genes such as mTOR, p53, NF-kappaB and BAD are all regulated through PI3K and Akt activation, making them attractive targets for broad downstream effects. Direct PI3K inhibition has demonstrated impressive tumor inhibition and regression in cell-line and animal models, and multiple agents including SF1126 are currently in clinical trials. Drugs such as perifosine that are specific for Akt are also in development. Combinations of these agents with existing therapies are rational approaches on the path to improving myeloma treatment.