Stromal cell-derived factor 1α mediates resistance to mTOR-directed therapy in pancreatic cancer.

ABSTRACT:

Purpose

The factors preventing the translation of preclinical findings supporting the clinical development mTOR-targeted therapy in pancreatic cancer therapy remain undetermined. Stromal cell.derived factor 1α (SDF-1α)-CXCR4 signaling was examined as a representative microenvironmental factor able to promote mTOR-targeted therapy resistance in pancreatic cancer.

Experimental design

Primary pancreas explant xenografts and in vitro experiments were used to perform pharmacodynamic analyses of SDF-1α-CXCR4 regulation of the mTOR pathway. Combinatorial effects of CXCR4, EGFR, and mTOR pharmacologic inhibition were evaluated in temsirolimus-resistant and -sensitive xenografts. Intratumoral gene and protein expressions of mTOR pathway effectors cyclin D1, c-Myc, and VEGF were evalu

SUBMITTER: Weekes CD 

PROVIDER: S-EPMC3432475 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature