The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/55813
Title:
The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer.
Authors:
Adamski, J K; Estlin, Edward J; Makin, Guy W J
Abstract:
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.
Affiliation:
School of Cancer and Imaging Studies, Faculty of Medical and Human Studies, University of Manchester, United Kingdom. JAdamski@picr.man.ac.uk
Citation:
The cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer. 2008, 34 (3):231-46 Cancer Treat. Rev.
Journal:
Cancer Treatment Reviews
Issue Date:
May-2008
URI:
http://hdl.handle.net/10541/55813
DOI:
10.1016/j.ctrv.2007.11.005
PubMed ID:
18207646
Type:
Article
Language:
en
ISSN:
0305-7372
Appears in Collections:
All Christie Publications ; Clinical and Experimental Pharmacology Group

Full metadata record

DC FieldValue Language
dc.contributor.authorAdamski, J K-
dc.contributor.authorEstlin, Edward J-
dc.contributor.authorMakin, Guy W J-
dc.date.accessioned2009-03-16T16:30:59Z-
dc.date.available2009-03-16T16:30:59Z-
dc.date.issued2008-05-
dc.identifier.citationThe cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer. 2008, 34 (3):231-46 Cancer Treat. Rev.en
dc.identifier.issn0305-7372-
dc.identifier.pmid18207646-
dc.identifier.doi10.1016/j.ctrv.2007.11.005-
dc.identifier.urihttp://hdl.handle.net/10541/55813-
dc.description.abstractExposure 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.en
dc.language.isoenen
dc.subjectHypoxiaen
dc.subjectChildhood Canceren
dc.subjectNovel Agentsen
dc.subject.meshAdaptation, Physiological-
dc.subject.meshCell Hypoxia-
dc.subject.meshChild-
dc.subject.meshDrug Delivery Systems-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshEnergy Metabolism-
dc.subject.meshGenomic Instability-
dc.subject.meshHumans-
dc.subject.meshHypoxia-Inducible Factor 1-
dc.subject.meshNeoplasms-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshSignal Transduction-
dc.titleThe cellular adaptations to hypoxia as novel therapeutic targets in childhood cancer.en
dc.typeArticleen
dc.contributor.departmentSchool of Cancer and Imaging Studies, Faculty of Medical and Human Studies, University of Manchester, United Kingdom. JAdamski@picr.man.ac.uken
dc.identifier.journalCancer Treatment Reviewsen

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