Biography and research overview
Over the last 10 years Dr Clarke’s research has contributed to the discovery of the structure and function of a key cancer molecule, Hsp90, and drugs which target this protein. The significance of this pioneering research was recognised by the award of the prestigious Cancer Research UK Translational Cancer Research Prize (2013) and Dr Clarke was a member of this team of senior scientists.
Dr Clarke takes particular responsibility for mechanistic molecular pharmacology studies and the discovery of biomarkers of drug action, with a special focus on molecular chaperones and the PI3 kinase pathway. He has a high level of expertise in the combined use of chemical tools and molecular genetic technologies to identify and validate new drug targets and to discover and validate predictive and mode of action biomarkers for drugs that inhibit these targets.
The molecular chaperone Hsp90 is a stress-regulated protein that contributes to protein quality control by maintaining the activity of client proteins that are fundamentally important in cancer. Inhibiting Hsp90 has pleiotropic effects, undermining cancer cell growth, survival and metastasis. Dr Clarke’s research has contributed to the discovery of drugs that target Hsp90. One of these drugs, AUY922, has shown promising activity in clinical trials in drug-resistant breast and non-small cell lung cancers.
Dr Clarke has also contributed to the research of teams developing drugs targeting oncogenic signal transduction, including the discovery of the leading PI3 kinase inhibitor GDC-0941, which is now showing promising activity in clinical trials.
Overall, Dr Clarke aims to contribute to the wider goal of the Cancer Research UK Cancer Therapeutics Unit to improve the lives of cancer patients through the discovery and development of personalised molecular medicines.