The prostate cancer research effort in PGJCCR is delivered by an experienced team of multidisciplinary researchers with a strong clinical and translational emphasis.
The clinical prostate research team is led by Prof Joe O'Sullivan along with Prof Suneil Jain working alongside NHS colleagues in particular Dr Darren Mitchell. The team is based at the Northern Ireland Cancer Centre and offers a comprehensive clinical trial portfolio to the prostate cancer population of Northern Ireland. As a team, we see more than 500 new prostate cancer patients per year, recruiting an average of 30% to clinical trials.
The main themes of our clinical research programme are:
- The optimisation of radiation therapy in the management of prostate cancer
- New therapeutics in metastatic castrate resistant prostate cancer (mCRPC)
- Radionuclide therapy in metastatic prostate cancer
- Biomarker discovery and precision prostate cancer therapy
We strongly believe in the importance of embedding clinical research within the health service and have been able to introduce some key service developments including intensity-modulated radiation therapy (IMRT), imaged guided radiation therapy (IGRT), stereotactic ablative radiotherapy (SABR), Radium-223, and high dose rate (HDR) brachytherapy through a clinical trial-based approach. The clinical academic team work closely with a number of key members of the NHS team including Prof Alan Hounsell (Radiotherapy Physics), Sandra Biggart (Radionuclide physics), NHS consultants Dr Darren Mitchell and Dr Lin Shum, as well as supported by the team of clinical nurse specialists. This work has been supported by the Prostate Cancer UK FASTMAN Movember Centre of Excellence (in collaboration with the University of Manchester).
In metastatic prostate cancer, Prof O’Sullivan was the Local Principal investigator on clinical trials of Radium-223 for prostate cancer (including the ALSYMPCA Phase 3 trial). These successful trials made Radium-223 the first radionuclide therapy to demonstrate survival benefit in metastatic cancer, and it is now approved for use in more than 50 countries (under the brand name Xofigo).
The team have also made significant contributions in other radiotherapy techniques. Through the CHHiP trials, we were involved in demonstrating the equivalence of hypofractionated radiotherapy (delivery of fewer, larger doses of radiotherapy) using advanced delivery techniques such as IMRT and IGRT. More recently, the SPORT trial (stereotactic radiotherapy to treat prostate cancer), led by Prof Jain, is the first of its kind in the UK to use SABR to enable prostate cancer patients to receive their full course of radiotherapy in five hospital visits instead of the typical 37. Involvement in these trials has enabled the translation and development of radiotherapy technologies in Northern Ireland, resulting in improved cure rates, reduced toxicity and increased efficiency of radical radiotherapy for all prostate cancer patients.
This clinically focussed research is complemented by our pre-clinical research led by Ian Mills and Karen McCloskey. The focus of pre-clinical research is on understanding how genomics, organelle biogenesis and cell signalling are impacted by cancer treatments, particularly radiotherapy, and affect the response of cancer cells and progression. This work is centred on prostate and bladder cancers.
Prof McCloskey’s research has unique strengths in characterising signalling required for normal bladder function and how that is altered both in bladder disease but also through toxicity associated with radiation therapy. In both bladder and prostate cancer she is focussing on how changes in ion channel expression and function impact on disease progression. Understanding toxicities and limiting their extent/impact is also a major goal of the BUStIN trial (trial investigating bladder volume consistency using ultrasound and biomarker analysis during prostate radiotherapy) headed by Joe O’Sullivan and Karen McCloskey.
Other pre-clinical studies are focussing on the impact of radiation therapy on the activity of stress response pathways and gatekeepers of stress response checkpoints, such as p53. We are evaluating molecular targets pre-clinically which can further amplify pro-apoptotic stress response signals to radiation-induced damage and restrict the evolution of resistant cells. To do so we are developing pre-clinical models from patient samples and working with in vivo models as well as in vitro. The amplitude of activation of the unfolded protein response/organelle function and the metabolic status of cancer cells appear to be particularly significant in this evolution and can be impacted both at the chromatin level and by targeting key enzymes and transcription factors that regulate these biologies.