Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

INTRODUCTION: Activation of the hypoxia response pathway is a feature of many tumours and is one of the key mechanisms associated with tumour growth, chemoresistance and radioresistance. The major component of the hypoxia response pathway is the heterodimeric transcription factor, hypoxia-inducible factor (HIF), which is upregulated in many human cancers. Therefore, HIF is an attractive therapeutic target and several strategies have been developed to target it. AREAS COVERED: Approaches used in targeting the hypoxia response pathway are discussed. Reviewed are agents that target upstream, directly and downstream of HIF, as well as some of the challenges in HIF-targeted therapy. EXPERT OPINION: Many of the therapeutic agents that are in clinical use inhibit downstream HIF target genes, but ideally a molecule specific to HIF will have a more potent effect in inhibiting multiple HIF pathways. However, many anti-HIF molecules have multiple targets, which may increase non-specific cytotoxicity. In addition, many anti-HIF agents cannot discriminate between the different isoforms of HIF-α. So, it is important to assess whether targeting both HIF-1α and HIF-2α or each subunit selectively will provide better therapeutic effects.

Original publication

DOI

10.1517/14728222.2012.674516

Type

Journal article

Journal

Expert Opin Ther Targets

Publication Date

05/2012

Volume

16

Pages

463 - 480

Keywords

Animals, Antineoplastic Agents, Basic Helix-Loop-Helix Transcription Factors, Drug Design, Gene Expression Regulation, Neoplastic, Humans, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Molecular Targeted Therapy, Neoplasms, Up-Regulation