Abstract
Solid tumours contain regions of very low oxygen concentrations that are said to be hypoxic. Hypoxia is a natural phenotype of solid tumours resulting from an imperfect vascular network. There are a number of consequences associated with tumour hypoxia including: resistance to ionising radiation, resistance to chemotherapy and the magnification of mutated p53. In addition tissue hypoxia has been regarded as a key factor for tumour aggressiveness and metastasis by activation of signal transduction pathways and gene regulatory mechanisms. It is clear that hypoxia in solid tumours promotes a strong oncogenic phenotype and is a phenomenon that occurs in all solid tumours. As such this provides a significant target for drug discovery particularly for tumour-targeting agents. A range of chemical classes (N-oxides, quinones, nitro-aromatics) have been explored as bioreductive agents that target tumour hypoxia. The most advanced agent, tirapazamine, is in phase III clinical trials in combination with cis-platin. The aim of this review is to give a brief overview of the current molecules and strategies being explored for targeting tumour hypoxia.
Keywords: Hypoxia, tumour targeting, bioreduction
Anti-Cancer Agents in Medicinal Chemistry
Title: Hypoxia: Targeting the Tumour
Volume: 6 Issue: 4
Author(s): Robert George Boyle and Stuart Travers
Affiliation:
Keywords: Hypoxia, tumour targeting, bioreduction
Abstract: Solid tumours contain regions of very low oxygen concentrations that are said to be hypoxic. Hypoxia is a natural phenotype of solid tumours resulting from an imperfect vascular network. There are a number of consequences associated with tumour hypoxia including: resistance to ionising radiation, resistance to chemotherapy and the magnification of mutated p53. In addition tissue hypoxia has been regarded as a key factor for tumour aggressiveness and metastasis by activation of signal transduction pathways and gene regulatory mechanisms. It is clear that hypoxia in solid tumours promotes a strong oncogenic phenotype and is a phenomenon that occurs in all solid tumours. As such this provides a significant target for drug discovery particularly for tumour-targeting agents. A range of chemical classes (N-oxides, quinones, nitro-aromatics) have been explored as bioreductive agents that target tumour hypoxia. The most advanced agent, tirapazamine, is in phase III clinical trials in combination with cis-platin. The aim of this review is to give a brief overview of the current molecules and strategies being explored for targeting tumour hypoxia.
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Cite this article as:
George Boyle Robert and Travers Stuart, Hypoxia: Targeting the Tumour, Anti-Cancer Agents in Medicinal Chemistry 2006; 6 (4) . https://dx.doi.org/10.2174/187152006777698169
DOI https://dx.doi.org/10.2174/187152006777698169 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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