Abstract

Professor Paul Workman is Harrap Professor of Pharmacology and Therapeutics at The Institute of Cancer Research (ICR) and Director of the ICR ’s Cancer Research UK Cancer Therapeutics Unit (CTU). He is also Deputy CEO of the ICR and Head of its Division of Cancer Therapeutics. He leads a large interdisciplinary research team that has been responsible for the discovery of 16 new drug candidates over the last 6 years, with 6 entering Phase I trials in ICR ’s partner hospital the Royal Marsden in the last 2 years, and abiraterone gaining regulatory approval in late stage prostate cancer. Paul’s research interests are in the design and application of chemical probes, the discovery and development of molecular cancer therapeutics aimed at ‘drugging the cancer genome’ and the development of personalized molecular medicines for cancer. Alongside drug discovery, Paul has led research to identify and utilize predictive and pharmacodynamic biomarkers and originated the now widely used concept of the ‘pharmacological audit trail.’ In this lecture he will outline the strategic approach to drug discovery taken in the non-profit CTU , then briefly exemplify this with reference to abiraterone, PI3 kinase and AKT /PKB inhibitors, and finally review in detail the progress of HSP90 molecular chaperone inhibitors from natural product tools to the discovery in CTU /Vernalis of VER -52296/NVP-AUY922 which is now in Phase II clinical trial having been licensed to Novartis. This is story that encapsulates all of the key elements of modern drug discovery and development, including structure-based design and biomarker-led clinical trials. Current and future challenges in drugging the cancer genome will be discussed.