Professor David Haigh, Lead Investigator
Despite over fifty years of research in the field of anticancer drug discovery, ranging from DNA modifying agents such as N-mustards and platinum cross-linking agents; anti-metabolite and natural products including Methatrexate and Paclitaxel to more recent anti-hormonal drugs such as Tamoxifen, the challenge of identifying clinically useful oncology medicines remains daunting. During the last twenty years, as knowledge of the heterogeneity of cancer as a disease has increased, greater emphasis has been placed on new molecularly-targeted drugs, designed to inhibit enzymes resulting from over-expression of aberrant genes, or that interfere with signalling pathways that are also related to aberrant gene expression. Some notable successes include Gleevec and Tykerb. As our understanding of the relationships between these genes and the biology of cancer continues to grow, new opportunities for targeted therapy will continue to emerge.
Working in synergy with members of both the Cancer Cell and Molecular Biology and the Experimental Cancer Medicine Divisions, the remit of the Drug Discovery group is to pursue these emerging novel and innovative biological targets through the early stages of the drug discovery process. These stages define the transition from basic molecular biological understanding of disease targets towards the identification of appropriate small-molecule “tool” and “hit” compounds, capable of modulating the biological activities of those targets and the initiation of “hit-to-lead” and early “lead-optimisation” research programmes. Research is currently focused on the discovery of inhibitors of protease enzymes and on disrupting protein-protein interactions, targets in several pathways associated with aberrant control of oncogenic activity, dysregulation of protein trafficking, control of nucleocytoplasmic transport or regulation of cellular apoptosis. Based on these initial drug discovery efforts, it is anticipated that molecules will emerge that may be developable into the next generation of clinical medicines. The multidisciplinary environment within CCRCB offers a significant opportunity for chemists, biologists and computer modellers to combine their expertise in-silico drug design, organic synthesis, bioassay design and screening, thus facilitating the drug discovery process.