Current research:
The focus of this group is the design, pre-clinical development and early clinical evaluation of agents directed against novel targets. In addition to Phase I trials, our research portfolio includes Phase II and III trials in lung cancer, breast cancer and endocrine tumours.

In recent years many new targets for cancer therapy have been identified and validated by Cancer Research UK and others. We have evaluated novel agents that target matrix metalloproteinases, growth factor activation, regulators of signal transduction and cell cycle control. As a Cancer Research UK Phase I Clinical Centre and National Translational Research Centre we are well placed to undertake the pharmacodynamic and pharmacokinetic assessment of such agents within a multi-disciplinary team setting. Critical to this is the ability to analyse tumour and normal tissue samples prior to, and following, treatment with a novel agent. To this end, we have developed methods to determine DNA damage and apoptosis in patients undergoing treatment with agents that target cdk2 and cyclins.

We are also conducting a Phase I evaluation of AQ4N, a hypoxically activated topoisomerase II inhibitor. Communication with the public and patients is part of the Cancer Research UK mission statement. Our group has conducted research on key elements of doctor/patient interactions and how these can be assessed objectively. We have developed validated methodology for objective assessment of physician/patient communication skills. This has been adopted by the General Medical Council and National Cancer Institute for training and formal assessment of clinical skills of oncologists.

Future projects:
Human AP endonuclease I (HAP 1) is a key enzyme in cellular protection from hypoxic stress with a role in repair of DNA damage caused by drugs and radiation. Inhibitors of HAP 1 would be valuable agents with which to explore the possibility of enhancing treatments of drug resistant tumours. We have developed, in collaboration with the Applied Development Laboratory (ADL), an automated HAP 1 assay that can be employed in high throughput screening for inhibitors of the enzyme. In conjunction with the Bimolecular Structure Unit and Imperial College we have identified lead compounds which are currently being evaluated in the pre-clinical setting. The use of specific and sensitive assessments of tumour and normal cell apoptosis following novel cancer therapies will be developed further and applied to a wide range of early clinical trials conducted by the group. The availability of Positron Emission Tomography to evaluate intra-tumoural metabolism will enhance the study of novel therapies.