PDF Version for Printing
The articles referenced in this Highlights section will be available online in HTML and PDF formats to all interested users at no charge until the next issue of Molecular Cancer Therapeutics is published. Click on the article title to view the complete article.
View the Table of Contents for the November 2007 issue of Molecular Cancer Therapeutics
Page 2817
Page 2828
Page 2879
Page 2900
With the advent of hypoxia targeted therapies in combination with hepatic artery ligation, the need for noninvasive hypoxia monitoring and therapeutic efficacy will become necessary. Brader and colleagues developed an orthotopic liver tumor model with a hypoxia-sensitive reporter system to monitor tumor hypoxia by noninvasive imaging. Their results demonstrated that the orthotopic reporter-transduced RH7777 Morris hepatomas are natively hypoxic and poorly perfused in this animal model, and that the magnitude of moderately severe hypoxia can be monitored using a HRE-responsive reporter system for both bioluminescence and PET imaging.
Toral-Barza et al. Page 3028 Extensive conservation of the ATP-binding sites of AGC kinases presents an impediment to the development of selective inhibitors. Lactoquinomycin and related pyranonaphthoquinones were found as a new class of potent and selective inhibitors of AKT/PKB. Through biochemical studies and enzyme mutagenesis, Toral-Barza and colleagues showed that these inhibitors targeted AKT via a novel allosteric mechanism that involves Cys-296 and Cys-310 residues of the T-loop. Lactoquinomycin inhibited cellular AKT substrate phosphorylation induced by growth factors, loss of PTEN, and myristoylated AKT. Co-expression of the AKT mutant C296A/C310A attenuated inhibitor-induced substrate dephosphorylation. These findings identified T-loop targeting as a new strategy to target AKT.
Page 3028