Increased glucose metabolism may occur in malignant tumours due to altered gene expression or a response to hypoxia. It has been shown that tumours with high levels of glycolysis, indicated by elevated lactate, are less responsive to radiotherapy. It is not clear whether this effect is caused by lactate itself or rather that high lactate is a surrogate for a radioresistant property such as hypoxia. Furthermore, we are not aware of studies that examine the manipulation of lactate production in tumours to alter radiation response. We propose a novel approach of metabolic targeting of HIF-1 to address these issues. HIF-1 is a major regulator of glycolysis and its inhibition would decrease malignant cell metabolism and could lead to a decrease in lactate production. The goal of this pre-clinical study was to evaluate metabolic targeting as a strategy of enhancing radiation response by inhibiting the HIF-1 transcription factor.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/31304 |
| Date | 14 December 2011 |
| Creators | Leung, Eric |
| Contributors | Hill, Richard, Wilson, Brian Campbell |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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