Galway University Hospital, Department of Haematology , Newcastle Road, Galway , Ireland.
Expert Opin Ther Targets. 2014 Aug;18(8):897-915. doi: 10.1517/14728222.2014.924507. Epub 2014 Jun 6.
Multiple myeloma remains an incurable malignancy with poor survival. Novel therapeutic approaches capable of improving outcomes in patients with multiple myeloma are urgently required. AKT is a central node in the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin signaling pathway with high expression in advanced and resistant multiple myeloma. AKT contributes to multiple oncogenic functions in multiple myeloma which may be exploited therapeutically. Promising preclinical data has lent support for pursuing further development of AKT inhibitors in multiple myeloma. Lead drugs are now entering the clinic.
The rationale for AKT inhibition in multiple myeloma, pharmacological subtypes of AKT inhibitors in development, available results of clinical studies of AKT inhibitors and suitable drug partners for further development in combination with AKT inhibition in multiple myeloma are discussed.
AKT inhibitors are a welcome addition to the armamentarium against multiple myeloma and promising clinical activity is being reported from ongoing trials in combination with established and/or novel treatment approaches. AKT inhibitors may be set to improve patient outcomes when used in combination with synergistic drug partners.
多发性骨髓瘤仍然是一种无法治愈的恶性肿瘤，患者生存率低。目前迫切需要新的治疗方法，以改善多发性骨髓瘤患者的预后。AKT 是磷脂酰肌醇 3-激酶/AKT/雷帕霉素靶蛋白信号通路的核心节点，在晚期和耐药性多发性骨髓瘤中高表达。AKT 促进多发性骨髓瘤中的多种致癌功能，这些功能可能具有治疗潜力。有前景的临床前数据为进一步开发 AKT 抑制剂治疗多发性骨髓瘤提供了支持。先导药物现已进入临床阶段。
探讨 AKT 抑制剂在多发性骨髓瘤中的作用机制、正在开发的 AKT 抑制剂的药理学亚型、AKT 抑制剂的临床研究结果以及与 AKT 抑制联合应用于多发性骨髓瘤的合适药物伙伴，以进一步开发。
AKT 抑制剂是对抗多发性骨髓瘤的有力武器，正在进行的联合现有和/或新型治疗方法的临床试验报告了有前途的临床活性。当与协同药物伙伴联合使用时，AKT 抑制剂有望改善患者的预后。
