Urological cancers
The Urology Research Group comprises a team of scientists and clinicians whose main focus is to study the biology of prostate cancer development and the progression of the disease. Our research is conducted at the clinical-laboratory interface.
Prostate cancer remains the most commonly diagnosed cancer in men in the UK, accounting for more than 10,000 male deaths per annum. With an ageing population, we urgently need better treatments for those patients with aggressive, life-limiting disease. For the development of such treatments, it is essential to further clarify the pathogenesis and mechanisms involved in the disease process.
Androgen receptor signalling mechanisms
Current therapies for prostate cancer aim to block the body’s production of testosterone and/or block the action of testosterone in the prostate. However, most prostate cancers recur and are no longer responsive to therapy.
We have detailed a number of novel regulatory proteins that are components of the androgen receptor signalling pathway. Our research involved inhibiting the functional capacity of these regulatory proteins; the key signalling pathways through the androgen receptor were diminished as a result, compromising cancer cell growth. In collaboration with other members of NICR, and industrial partners, we are developing small molecules that can specifically target these regulatory proteins to improve future clinical outcome for prostate cancer patients with advanced disease.
Manipulation of growth factor-mediated signalling
We continue to make important progress in our understanding of the role of the MEK5/ERK5 pathway in aggressive prostate cancer. In addition, we have consolidated our research programme by forming strategic collaborations within the university to develop specific small molecule inhibitors of the MEK5/ERK5 pathway for Phase I clinical trials in patients with advanced prostate cancer.
We are also re-investigating the importance of the EGF receptor family in prostate cancer, concentrating on the HER2/HER3 heterodimer, which has been demonstrated to be involved in a novel mechanism of androgen receptor activation.
Urological stem cells
In a number of cancers it is now becoming clear that specialised cells, known as cancer stem cells, are involved in tumour maintenance and renewal. Cancer stem cells and normal stem cells share common properties, and considering cancer stem cells may potentially have arisen from normal cells, it is essential to characterise and identify key differences in their pathways.
Indeed, by using a variety of approaches, based on in situ, in vitro and in vivo studies, we are currently investigating urological tissues. We aim to translate such findings to develop targeted treatments that eliminate the cancer stem cells without compromising normal cells. Furthermore, understanding normal stem cell function will aid tissue regeneration for patients with diseased organs that require replacement.
