Abstract

[...]AKT1 activation decreases tumor metastatic dissemination but promotes mammary tumorigenesis in mouse models, whereas AKT2 primarily increases tumor metastasis in those models [10–12]. [...]specific AKT isoforms have been demonstrated to be drivers in particular cancers. Furthermore, activating mutations in AKT1 are much more common than those in AKT2 or AKT3 with for example the E17K activating mutation in the PH domain being more than 25 fold less frequent in AKT2 or AKT3 than in AKT1. [...]inhibition of specific AKT isoforms in particular cancers at specific stages provides an approach that could be used to target the effects of cancer drivers and would overcome the disadvantages of pan-AKT inhibition in terms of toxicity. The pan antibodies for AKT or pAKT recognized AKT3 (Fig. 1a, right panel). Because no phospho-AKT3 antibody is available at this time, we therefore focused on isoform-specific expression and phosphorylation of AKT1 and AKT2, the two ubiquitously expressed AKT isoforms [24]. First-in-man clinical trial of the oral pan-AKT inhibitor MK-206 in patients with advanced solid tumors.

Details

Title
AKT isoform-specific expression and activation across cancer lineages
Author
Wang, Jue; Zhao, Wei; Guo, Huifang; Fang, Yong; Stockman, Sarah Elizabeth; Bai, Shanshan; Ng, Patrick Kwok-Shing; Yang, Li; Yu, Qinghua; Lu, Yiling; Kang Jin Jeong; Chen, Xiaohua; Gao, Meng; Liang, Jiyong; Li, Wentao; Tian, Xingsong
Publication year
2018
Publication date
2018
Publisher
BioMed Central
e-ISSN
14712407
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2071945384
Copyright
Copyright © 2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the terms of the License.