当前位置: X-MOL 学术Mol. Cancer Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Emerging Roles for AKT Isoform Preference in Cancer Progression Pathways
Molecular Cancer Research ( IF 5.2 ) Pub Date : 2021-08-01 , DOI: 10.1158/1541-7786.mcr-20-1066
Seamus E Degan 1 , Irwin H Gelman 1
Affiliation  

The phosphoinositol-3 kinase (PI3K)–AKT pathway is one of the most mutated in human cancers, predominantly associated with the loss of the signaling antagonist, PTEN, and to lesser extents, with gain-of-function mutations in PIK3CA (encoding PI3K-p110α) and AKT1. In addition, most oncogenic driver pathways activate PI3K/AKT signaling. Nonetheless, drugs targeting PI3K or AKT have fared poorly against solid tumors in clinical trials as monotherapies, yet some have shown efficacy when combined with inhibitors of other oncogenic drivers, such as receptor tyrosine kinases or nuclear hormone receptors. There is growing evidence that AKT isoforms, AKT1, AKT2, and AKT3, have different, often distinct roles in either promoting or suppressing specific parameters of oncogenic progression, yet few if any isoform-preferred substrates have been characterized. This review will describe recent data showing that the differential activation of AKT isoforms is mediated by complex interplays between PTEN, PI3K isoforms and upstream tyrosine kinases, and that the efficacy of PI3K/AKT inhibitors will likely depend on the successful targeting of specific AKT isoforms and their preferred pathways.

中文翻译:

AKT 异构体偏好在癌症进展途径中的新兴作用

磷酸肌醇 3 激酶 (PI3K)-AKT 通路是人类癌症中突变最多的途径之一,主要与信号拮抗剂 PTEN 的丢失有关,在较小程度上与 PIK3CA 中的功能获得突变(编码 PI3K -p110α) 和 AKT1。此外,大多数致癌驱动途径激活 PI3K/AKT 信号传导。尽管如此,靶向 PI3K 或 AKT 的药物在临床试验中作为单一疗法在对抗实体瘤方面表现不佳,但有些药物在与其他致癌驱动因子的抑制剂(如受体酪氨酸激酶或核激素受体)联合使用时已显示出疗效。越来越多的证据表明,AKT 同种型 AKT1、AKT2 和 AKT3 在促进或抑制致癌进展的特定参数方面具有不同且通常不同的作用,但很少有同种型首选底物的特征。
更新日期:2021-08-04
down
wechat
bug