Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers.

ABSTRACT:

Purpose

Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported.

Methods and materials

We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras(G12D)-induced and T

SUBMITTER: Zeng J 

PROVIDER: S-EPMC4145860 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature