Multimodal targeting of tumor vasculature and cancer stem-like cells in sarcomas with VEGF-A inhibition, HIF-1α inhibition, and hypoxia-activated chemotherapy.

ABSTRACT: Vascular endothelial growth factor A (VEGF-A) inhibition with pazopanib is an approved therapy for sarcomas, but likely results in compensatory pathways such as upregulation of hypoxia inducible factor 1α (HIF-1α). In addition, cancer stem-like cells can preferentially reside in hypoxic regions of tumors and be resistant to standard chemotherapies. In this study, we hypothesized that the combination of VEGF-A inhibition, HIF-1α inhibition, and hypoxia-activated chemotherapy with evofosfamide would be an effective multimodal strategy. Multimodal therapy was examined in one genetically engineered and two xenograft mouse models of sarcoma. In all three models, multimodal therapy showed greater efficacy than any single agent therapy or bimodality therapy in blocking tumor growth. Even after ce

SUBMITTER: Yoon C 

PROVIDER: S-EPMC5189991 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature