Research within the Cancer Biomarkers and Prevention Section is primarily focused on the development of markers of exposure, effect, diagnosis, therapy and susceptibility, whilst the development of cancer chemopreventive strategies involves the characterisation of diet-derived agents, investigation of their mechanisms of action and efficacy assessment in preclinical models of carcinogenesis. A key feature of the Section is the unique combination of chemical, biochemical, pharmacokinetic, pharmacodynamic and oncological expertise. It is excellently equipped for work involving analytical chemistry, molecular epidemiology, cellular and molecular biology, drug metabolism, radiation studies, in vivo models of carcinogenesis, pharmacokinetic studies and small scale clinical trials with access to clinical samples.
Biomarkers are identified based on mechanistic findings, and include the determination of DNA adducts and oxidative DNA damage, the use of cell free plasma DNA, determination of altered gene expression, microRNAs or specific protein markers, and the application of proteomic and metabonomic methods. Ideal markers reflect the status of the carcinogenic process, identify at-risk individuals and predict disease occurrence, and can as well determine the efficacy of chemoprevention and therapy. Applications for these biomarkers include molecular epidemiology studies in humans exposed to environmental carcinogens, assessment of efficacy of cancer chemopreventive interventions in at-risk populations, and assessment of treatment efficacy.
The most promising cancerpreventive agents are taken through to pilot clinical trials for evaluation of toxicity/tolerability and pharmacokinetic and pharmacodynamic properties. Based on the pharmacokinetic properties and any toxicity established for the compound, together with the biomarker data, novel chemical structures for cancerpreventive agents are also being identified and synthesised for evaluation. Resveratrol, a constituent of red wine, and tricin, a flavone found in rice bran, are two agents currently being studied.
Radiotherapy and chemotherapy are two principal modalities of cancer treatment. For radiation and many chemotherapy drugs, genomic DNA is the primary cellular target for the damaging effects of these agents, thought to be responsible for cancer killing cells. To better understand, judge and improve treatment efficacy, the Section’s research explores the mechanisms of these damaging interactions and develops methods for the accurate measurement of the damage induced. Emphasis is on studying clinically relevant doses and on translational research with anticipated patient benefit.
Members of academic staff based in the Cancer Chemoprevention Group are:
- Professor Karen Brown
- Professor Andreas Gescher
- Dr Don J L Jones
- Dr Alessandro Rufini
- Professor Will Steward
- Professor Anne Thomas
Research within the Section is funded from a variety of sources, including: