Duncan Jodrell scientific summary

Pharmacology and drug development

Previous and current research

The composition of the multi-disciplinary Cancer Research UK Pharmacology and Drug Development Group and its close links with the Early Phase Trials Team based in Addenbrooke's Hospital, facilitates the discovery, preclinical and clinical development of novel anti-cancer drugs, i.e., truly 'bench to bedside' or translational research.

Drug discovery projects have involved the development of ruthenium based organometallic compounds, novel pyrrolo-benzodiazepine based, sequence specific, DNA binding agents. Compounds have been developed which are active in laboratory models. Investigation of the downstream effects of these compounds are ongoing.

Early stage (phase I, phase II) clinical studies are performed in purpose built facilities at Addenbrooke's Hospital and the Group provides laboratory support for the early clinical development (phase I and II) of novel agents and for PK/PD studies involving drugs already established as therapies for cancer.

Collaborations exist with other groups within the University of Edinburgh, around the UK (through the Cancer Research UK Drug Development Office) and internationally, through membership of the Pharmacology and Molecular Mechanisms (PAMM) Group of the EORTC.

Future projects

The identification of factors, both pharmacokinetic and molecular, which predict outcome in patients receiving novel agents, leading to the development of individualised treatment strategies. Current work is focussing on the transport properties of DNA interactive drugs (PBDs), the metabolism and downstream effects of existing drugs for patients with colorectal cancer (e.g. irinotecan, oxaliplatin and capecitabine), including DNA damage recognition pathways. Metabolism pathways for capecitabine are being mapped using non-invasive imaging techniques.

It is hoped that these approaches will lead to clinical confirmation of our laboratory discoveries.