Metronomic doxorubicin blocks HIF-1α-mediated responses in sarcomas and augments the effects of anti-VEGF-A therapy

ABSTRACT: Increased levels of hypoxia and hypoxia inducible factor 1α (HIF-1α) in human sarcomas correlate with tumor progression and radiation resistance. Prolonged anti-angiogenic therapy of tumors can delay tumor growth but may also increase hypoxia and HIF-1α activity. In our recent clinical trial, treatment with the anti-vascular endothelial growth factor A (VEGF-A) antibody, bevacizumab, followed by a combination of bevacizumab and radiation led to near complete necrosis in nearly half of sarcomas. Gene set enrichment analysis of microarrays from pre-treatment biopsies found the Gene Ontology category “Response to hypoxia” was upregulated in poor responders, and hierarchical clustering based on 140 hypoxia-responsive genes separated poor responders from good responders. The most commonly used

ORGANISM(S): Homo sapiens

SUBMITTER: Peter Park 

PROVIDER: E-GEOD-31715 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress