Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Dis Model Mech. 2010 Nov-Dec;3(11-12):705-20. doi: 10.1242/dmm.004671. Epub 2010 Oct 12.
AKT hyperactivation is a common event in human cancers, and inhibition of oncogenic AKT activation is a major goal of drug discovery programs. Mouse tumor models that replicate AKT activation typical of human cancers provide a powerful means by which to investigate mechanisms of oncogenic signaling, identify potential therapeutic targets and determine treatment regimes with maximal therapeutic efficacy. This Perspective highlights recent advances using in vivo studies that reveal how AKT signaling supports tumor formation, cooperates with other mutations to promote tumor progression and facilitates tumor-cell dissemination, focusing on well-characterized prostate carcinoma mouse models that are highly sensitive to AKT activation. The implications of these findings on the therapeutic targeting of AKT and potential new drug targets are also explored.
AKT 过度激活是人类癌症中的常见事件，抑制致癌 AKT 激活是药物发现计划的主要目标。复制人类癌症中典型 AKT 激活的小鼠肿瘤模型为研究致癌信号转导机制、确定潜在治疗靶点以及确定具有最大治疗效果的治疗方案提供了一种强大的手段。本观点重点介绍了最近使用体内研究取得的进展，这些研究揭示了 AKT 信号如何支持肿瘤形成、与其他突变协同促进肿瘤进展并促进肿瘤细胞扩散，重点介绍了对 AKT 激活高度敏感的高度特征性前列腺癌小鼠模型。还探讨了这些发现对 AKT 治疗靶向和潜在新药物靶点的意义。
