Biomarkers and Cancer Prevention
Effective cancer prevention depends on an understanding of the causes of cancer and the development of reliable biomarkers to detect early signs of the disease and follow treatment efficacy. Cancer chemoprevention encompasses intervention at all stages of the disease by pharmacological means to inhibit the onset of preneoplasia or primary tumour as well as progression and development of metastasis in late stage disease. Work in the group is focussed on;
- The identification of optimal agents for effective and safe intervention.
- A detailed understanding of their mechanisms of action.
- Effective means of selecting 'at risk' individuals or populations.
- Assessment of clinical efficacy in the short and medium term.
To improve chances of success in future trials, detailed knowledge of the mechanistic, pharmaceutical and pharmacological issues associated with promising novel agents needs to be coupled with reliable biomarkers and careful choice of the most appropriate recipients for intervention.
Research in the Biomarkers and Cancer Prevention sub-theme has focussed on biomarkers of exposure to putative carcinogens and detection of early biological effect, as well as mechanisms of action of chemopreventive agents. Naturally occuring diet-derived agents with promising cancer chemopreventive properties have been advanced to rodent testing and early clinical evaluation. Prevention efforts have focused on gastro-intestinal and prostate malignancies, but bladder, breast and pancreatic cancer are also under study. Work by theme participants also embraces increasing evidence that dietary agents may be effective in combination with chemotherapeutic drugs and/or radiation by enhancing efficacy or reducing toxicity.
The group has identified several agents, including resveratrol, curcumin, diindolylmethane, tricin and anthocyanins worthy of further investigation in human chemoprevention trials. Our recent studies have provided preclinical mechanistic information and data on safety, pharmacokinetics and early pharmacodynamics in humans. Key priorities for this group are;
- To gain a better understanding of the mechanisms of action of agents before they are chosen for definitive evaluation in humans.
- To develop biomarkers of response to aid the choice of optimal agents and to identify the most appropriate dosing regimen and to follow trials subjects for an early readout of potential efficacy.
- To develop complimentary biomarkers of individual cancer risk and carcinogenesis that can be used in cancer prevention and for earlier disease diagnosis.
- Development of an optimal preclinical and early clinical strategy which maximises the chance of identifying clinically effective agents.
- Definition of the most relevant chemopreventive mechanisms of action for a given target tissue and agent.
- Development of robust biomarkers of carcinogen exposure and/or susceptibility to cancer development to allow selection of appropriate individuals/populations for intervention.
- Development and validation of robust biomarkers of chemopreventive efficacy.
- Identification of intervention regimes worthy of clinical trial.
Non-Clinical: Karen Brown, Marcus Cooke, Mark Evans, Peter Farmer, Andy Gescher, Paul Jenkins, Don JL Jones, G Don Jones, Marina Kriajevska, Maggie Manson, Howard Pringle, Stewart Sale, Jacqui Shaw, and Raj Singh.