The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer.
Affiliation
School of Cancer and Imaging Studies, Faculty of Medical and Human Studies, University of Manchester, United Kingdom. JAdamski@picr.man.ac.ukIssue Date
2008-05
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Show full item recordAbstract
Exposure of tumour cells to reduced levels of oxygen (hypoxia) is a common finding in adult tumours. Hypoxia induces a myriad of adaptive changes within tumour cells which result in increased anaerobic glycolysis, new blood vessel formation, genetic instability and a decreased responsiveness to both radio and chemotherapy. Hypoxia correlates with disease stage and outcome in adult epithelial tumours and increasingly it is becoming apparent that hypoxia is also important in paediatric tumours. Despite its adverse effects upon tumour response to treatment hypoxia offers several avenues for new drug development. Bioreductive agents already exist, which are preferentially activated in areas of hypoxia, and thus have less toxicity for normal tissue. Additionally the adaptive cellular response to hypoxia offers several novel targets, including vascular endothelial growth factor (VEGF), carbonic anhydrase, and the central regulator of the cellular response to hypoxia, hypoxia inducible factor-1 (HIF-1). Novel agents have emerged against all of these targets and are at various stages of clinical and pre-clinical development. Hypoxia offers an exciting opportunity for new drug development that can include paediatric tumours at an early stage.Citation
The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer. 2008, 34 (3):231-46 Cancer Treat. Rev.Journal
Cancer Treatment ReviewsDOI
10.1016/j.ctrv.2007.11.005PubMed ID
18207646Type
ArticleLanguage
enISSN
0305-7372ae974a485f413a2113503eed53cd6c53
10.1016/j.ctrv.2007.11.005
Scopus Count
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