Combining the multitargeted tyrosine kinase inhibitor vandetanib with the antiestrogen fulvestrant enhances its antitumor effect in non-small cell lung cancer.

ABSTRACT:

Introduction

Estrogen is known to promote proliferation and to activate the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF) is a known estrogen responsive gene in breast cancer. We sought to determine whether the VEGF pathway is also regulated by estrogen in lung cancer cells, and whether combining an inhibitor of the ER pathway with a dual vascular endothelial growth factor receptor (VEGFR)/EGFR inhibitor would show enhanced antitumor effects.

Methods

We examined activation of EGFR and expression of VEGF in response to β-estradiol, and the antitumor activity of the multitargeted VEGFR/EGFR/RET inhibitor, vandetanib, when combined with the antiestrogen fulvestrant both in vitro and in vivo.

Results</

SUBMITTER: Siegfried JM 

PROVIDER: S-EPMC3288546 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature