Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models.

ABSTRACT:

Purpose

Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single-agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor, OSI-906, in combination with a mitogen-activated protein (MAP)-ERK kinase (MEK) 1/2 inhibitor based on evidence that the MAP kinase pathway was upregulated in colorectal cancer cell lines that were resistant to OSI-906.

Experimental design

The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126 were analyzed both as single agents and in combination in 13 colorectal cancer cell lines in vitro. Apoptosis, downstream effector proteins, and

SUBMITTER: Flanigan SA 

PROVIDER: S-EPMC3843359 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature