Abstract:
:Darbepoetin alfa (Aranesp), Amgen) is a novel erythropoiesis-stimulating protein with a serum half-life longer than recombinant human erythropoietin (Epo), used in the treatment of cancer-associated anaemia. Anaemia is known to adversely affect prognosis and response to treatment in cancer patients. Solid tumours contain regions of hypoxia due to poor vascular supply and cellular compaction. Although hypoxic stress usually results in cell death, hypoxia-resistant tumour cells are genetically unstable and often acquire a drug-resistant phenotype. Increasing tumour oxygenation and perfusion during treatment could have the doubly beneficial outcome of reducing the fraction of treatment-resistant cells, while increasing drug delivery to previously hypoxic tissue. In this study, we examined the effect of darbepoetin alfa on chemotherapy sensitivity and delivery in an in vivo model of Lewis lung carcinoma, shown here to express the Epo receptor (EpoR). We identified that weekly darbepoetin alfa treatment, commencing 10 days before chemotherapy, resulted in a significant reduction in tumour volume compared to chemotherapy alone. This was mediated by the prevention of anaemia, a reduction in tumour hypoxia and a concomitant increase in drug delivery. Darbepoetin alfa treatment alone did not modulate the growth of the EpoR-expressing tumour cells. This study identifies an important role for darbepoetin alfa in increasing the therapeutic index of chemotherapy.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Shannon AM,Bouchier-Hayes DJ,Condron CM,Toomey Ddoi
10.1038/sj.bjc.6602685subject
Has Abstractpub_date
2005-07-25 00:00:00pages
224-32issue
2eissn
0007-0920issn
1532-1827pii
6602685journal_volume
93pub_type
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journal_title:British journal of cancer
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journal_title:British journal of cancer
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章
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更新日期:1970-09-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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