Current research:
This group works on the growth factors and signalling pathways involved in human tumour angiogenesis. The clinical application of these studies relates mainly to breast and bladder cancer. We have developed methods to quantify angiogenesis in primary human cancers (Fox et al., Lancet Oncology 2001; 2: 278). and have shown that high microvessel density is associated with poor prognosis, micro-metastasis and resistance to drug therapy. Hypoxia has emerged as a key factor regulating angiogenesis (Harris, Nature Reviews Cancer 2002; 2: 38) and a major part of the group¿s work is on the pathways regulated by hypoxia, their role in cancer biology and as therapeutic targets.

Future projects:
From gene arrays analysing specific hypoxia regulated pathways, we have found that carbonic anhydrase IX, a novel transmembrane carbonic anhydrase, is up regulated in cancer and may be critical in regulating pH. Specific apoptotic pathways induced by hypoxia involving Bnip3 is also commonly up regulated in many tumour cell lines. Both these pathways are being investigated as potentially important biochemical pathways regulated by hypoxia which are also therapeutic targets. The role of hypoxia in regulating vascular differentiation and notch signalling is being studied for vascular targeting. There are two major transcription factors regulated by hypoxia, HIF-1 and HIF-2, which have different patterns of cellular expression and the roles of these two pathways are being studied.