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Ascorbate-mediated regulation of HIF-1 mediated tumour growth and angiogenesis

37 months
Approved budget:
Professor Margreet Vissers
Health issue:
Cancer (oncology)
Proposal type:
Lay summary
Hypoxia-inducible factor-1 (HIF-1) is a protein present in all cells that controls gene expression in response to environmental stress, particularly a lack of oxygen or nutrients. Such stresses are common in rapidly growing tumours where activation of HIF-1 promotes growth and survival and resistance to chemotherapy. Control of HIF-1 activity occurs through enzymes called hydroxylases that need vitamin C for activity. It is known that low vitamin C levels result in HIF-1 activation and, conversely, increasing vitamin C supply could work to limit the rate of tumour growth and enhance the response to chemotherapy. In this study we aim to test this hypothesis in a mouse model of vitamin C deficiency, in which we can carefully control the amount of vitamin C delivery. The effect of high-dose vitamin C on tumour growth and chemotherapy responsiveness will be determined.