Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity.
Journal Article (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