We are interested in addressing unanswered questions about the role of the physical and chemical tumour microenvironment in cancer development and progression.
For example, free radicals, including reactive oxygen species (ROS), are generated as a normal by-product of respiration and play an important role in intracellular and paracrine signalling in healthy tissue. These free radicals are normally detoxified by both enzymatic and non-enzymatic antioxidant systems. Oxidative stress, and eventually cell death, occurs when the concentration of free radicals exceeds the capacity of intracellular antioxidant systems to detoxify them. Cancers of the lung and gastrointestinal tract frequently arise from sites of chronic inflammation, where the sustained oxidative environment can damage healthy epithelial cells and lead to malignant transformation. Once transformed, the aberrant metabolism and proliferation of cancer cells in many different cancers, combined with areas of necrosis due to poor oxygen supply and inflammatory cell infiltration, lead to far higher levels of ROS.
Cancer cells must therefore adapt quickly in order to survive and continue to proliferate in the tumour mass. They achieve this via two mechanisms: first, they upregulate their antioxidant capacity to detoxify ROS; and second, they stimulate angiogenesis, the growth of new blood vessels from surrounding host vasculature, to improve the supply of oxygen and nutrients to the developing tumour. Understanding the influence of antioxidant capacity and tumour oxygenation on disease aggressiveness could therefore aid the development of biomarkers of early disease.
Emma Brown, Dale Waterhouse, Judith Weber, Dr Joanna Brunker.
Dr Christian Frezza (MRC Cancer Unit, University of Cambridge); Prof. Mike Murphy (Mitochondrial Biology Unit, University of Cambridge); Dr Andre Neves, Prof. Kevin Brindle, Dr Lexi Haslehurst, Prof. Bruce Ponder (CRUK CI); Prof. Kaye Williams (University of Manchester).