Targeting hypoxia and angiogenesis through HIF-1alpha inhibition.

Abstract:

:Hypoxia is an important phenomenon in the tumor microenvironment. Hypoxic tumors are more aggressive and resistant to anti-neoplastic treatments. HIF-1alpha plays a major role in the response of tumors to hypoxia, and it is mainly responsible for the "angiogenic switch". HIF-1alpha contributes to tumor aggressiveness, invasiveness, and resistance to radiotherapy and chemotherapy. Targeting HIF-1alpha is an attractive strategy, with the potential for disrupting multiple pathways crucial for tumor growth. We review recent findings on the potential efficacy of small molecules to downregulate HIF-1alpha. These promising drugs inhibit HIF-1alpha synthesis or transcriptional activity by blocking a variety of steps in several different signaling pathways. Blocking HIF-1alpha activity should not only downregulate tumor angiogenesis, but also interfere with glycolytic metabolism and tumor cell growth. This strategy could also improve the efficiency of established tumor therapies.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Diaz-Gonzalez JA,Russell J,Rouzaut A,Gil-Bazo I,Montuenga L

doi

10.4161/cbt.4.10.2195

keywords:

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

1055-62

issue

10

eissn

1538-4047

issn

1555-8576

pii

2195

journal_volume

4

pub_type

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