Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas.

ABSTRACT:

Background

Human sarcomas with a poor response to vascular endothelial growth factor-A (VEGF-A) inhibition and radiation therapy (RT) have upregulation of hypoxia-inducible factor 1α (HIF-1α) and HIF-1α target genes. This study examines the addition of the hypoxia-activated chemotherapy TH-302 to VEGF-A inhibition and RT (a.k.a. trimodality therapy).

Methods

Trimodality therapy was examined in two xenograft models and in vitro in tumour endothelial cells and sarcoma cell lines.

Results

In both mouse models, VEGF-A inhibition and radiation showed greater efficacy than either therapy alone in slowing sarcoma growth. When TH-302 was added, this trimodality therapy completely blocked tumour growth with tumours remaining dormant for over 3 months after cessation of therapy

SUBMITTER: Yoon C 

PROVIDER: S-EPMC4647529 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature