Hypoxia-Inducible PIM Kinase Expression Promotes Resistance to Antiangiogenic Agents.

ABSTRACT: Purpose: Patients develop resistance to antiangiogenic drugs, secondary to changes in the tumor microenvironment, including hypoxia. PIM kinases are prosurvival kinases and their expression increases in hypoxia. The goal of this study was to determine whether targeting hypoxia-induced PIM kinase expression is effective in combination with VEGF-targeting agents. The rationale for this therapeutic approach is based on the fact that antiangiogenic drugs can make tumors hypoxic, and thus more sensitive to PIM inhibitors.Experimental Design: Xenograft and orthotopic models of prostate and colon cancer were used to assess the effect of PIM activation on the efficacy of VEGF-targeting agents. IHC and in vivo imaging were used to analyze angiogenesis, apoptosis, proliferation,

SUBMITTER: Casillas AL 

PROVIDER: S-EPMC6214353 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature