Targeted Cancer Therapy
10 March 2008 - At The Institute, a new era of drug development is underway which seeks to exploit our newly acquired knowledge of the molecular mechanisms that drive cancer. An exciting target for cancer drug development is a so-called chaperone protein termed HSP90. HSP90 helps to maintain the shape, stability and function of a variety of molecules, a large number of which play critical roles in the development of cancer. Therefore, when HSP90 is inhibited many different cancer-causing proteins and pathways are affected at the same time – giving a powerful ‘combinatorial’ effect. If the function of HSP90 can be inhibited, then the processes by which cancer cells grow and spread can be shutdown.
Professor Paul Workman, Director of the Cancer Research UK Centre for Cancer Therapeutics, and his team are developing drugs to inhibit HSP90 in order to achieve this aim. Professor Workman summarises progress to date; “Using high-throughput screening and structure based design we have identified a novel series of potent and selective inhibitors of HSP90. In order to progress development of these potential drugs, we teamed up with the biotechnology company Vernalis and the pharmaceutical giant Novartis. The success of this project, which benefited from structural biology input from Professor Laurence Pearl’s team at The Institute, led to one of our HSP90 drugs entering clinical trial in September 2007. The Royal Marsden is involved in this trial and a second drug has also entered development.
“We are excited about the prospects for HSP90 inhibitors because these will simultaneously block many of the important processes that are essential for cancer cells to survive. Thus, HSP90 drugs have potential for broad activity across many tumour types and should minimise the opportunity for drug resistance to develop.”
Professor Paul Workman leads the Signal Transduction and Molecular Pharmacology Team in The Institute's Section of Cancer Research UK Centre for Cancer Therapeutics
