Professor Tim Harrison, Lead Investigator
It has become increasingly clear that rather than being a single disease, cancer is a heterogeneous collection of diseases. It therefore follows that in order to diagnose and treat cancer effectively, strategies for patient selection must be combined with the development of molecularly targeted therapeutics so that patients can receive the drug or combination of drugs which is most appropriate for the treatment of their disease, at the appropriate time.
This approach necessitates the involvement of multi-disciplinary teams of basic researchers and clinicians, working within an infrastructure which allows for effective knowledge transfer.
In June 2013, a new industrial-academic drug discovery collaboration was established within the Centre for Cancer Research and Cell Biology (CCRCB). This partnership integrates both academic and industrial scientists to facilitate the translation of basic research discoveries into products which can ultimately derive value for patients. Working in close partnership with researchers from across the University and local hospitals, as well as with external researchers, the mission of the Drug Discovery group is to identify molecular targets which are relevant to disease and to develop strategies to modulate their function. Working closely with colleagues within the Centre (which includes the new Northern Ireland Molecular Pathology Laboratory and NI Biobank), a strong emphasis will be placed on the early development of biomarkers, both for patient selection, and for determining the relationship between drug pharmacokinetics and the associated pharmacodynamic response.
Key to the progression of any drug discovery programme is the identification of a chemical compound (either small molecule or protein based) which can interact with the target. This drug “hit” is then optimised to provide a compound (often termed a preclinical candidate) which has the potency and specificity to interact with the target at a therapeutic concentration which does not cause unacceptable side effects. This candidate molecule is further evaluated in pre-clinical development studies before progressing into clinical trials.
The capabilities of the Drug Discovery group include:
- Medicinal chemistry expertise in hit identification, hit to lead and lead optimisation
- Biology expertise in target validation and assay development using multiple formats
- Fragment screening (using a range of orthogonal biophysical techniques)
- Computer aided drug design
- Measurement and interpretation of Absorption, Distribution, Metabolism and Excretion (ADME) and physicochemical properties of molecules
- State of the art compound storage and data management facilities
- Pre-clinical and clinical project management
- International network of collaborators and outsourced service providers.
Research is currently focussed on the discovery of inhibitors of ubiquitin specific proteases and other ligases involved in the ubiquitin-proteasome system, as well as other protease targets shown to be involved in cancer progression. There is also a strong interest in developing new strategies for the disruption of protein-protein interactions, using both small molecules and peptides, and in the development of novel delivery vehicles for the specific targeting of therapeutic agents to tumours. Based on these drug discovery capabilities, it is anticipated that molecules will emerge that may be developable into the next generation of clinical medicines. The projects originate both from the CCRCB and other Schools within QUB. The multidisciplinary environment within the Centre for Cancer Research and Cell Biology, itself situated within easy reach of other research QUB faculties and Clinical Centres, offers an exciting opportunity for chemists, biologists, bioinformaticians, physicists, radiographers and clinicians to combine their expertise to facilitate the drug discovery process.