Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.

Journal Article

We have previously shown that radiation increases HIF-1 activity in tumors, causing significant radioprotection of the tumor vasculature. The impact that HIF-1 activation has on overall tumor radiosensitivity, however, is unknown. We reveal here that HIF-1 plays an important role in determining tumor radioresponsiveness through regulating four distinct processes. By promoting ATP metabolism, proliferation, and p53 activation, HIF-1 has a radiosensitizing effect on tumors. Through stimulating endothelial cell survival, HIF-1 promotes tumor radioresistance. As a result, the net effect of HIF-1 blockade on tumor radioresponsiveness is highly dependent on treatment sequencing, with "radiation first" strategies being significantly more effective than the alternative. These data provide a strong rationale for pursuing sequence-specific combinations of HIF-1 blockade and conventional therapeutics.

Full Text

Duke Authors

Cited Authors

  • Moeller, BJ; Dreher, MR; Rabbani, ZN; Schroeder, T; Cao, Y; Li, CY; Dewhirst, MW

Published Date

  • August 2005

Published In

Volume / Issue

  • 8 / 2

Start / End Page

  • 99 - 110

PubMed ID

  • 16098463

International Standard Serial Number (ISSN)

  • 1535-6108

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2005.06.016

Language

  • eng

Conference Location

  • United States