Including bladder, penile, prostate, renal, and urinary tract cancers
Genitourinary (GU) cancers encompass all cancers associated with the urinary tract and male reproductive glands. This includes bladder, penile, prostate, renal, and urinary tract cancers. Research in GU cancer in Manchester covers basic laboratory research through to translational and clinical trials. Navigate to the different genitourinary cancers to discover more about Manchester activities using the links below.
The heart of our prostate cancer research is the FASTMAN Movember Centre of Excellence, which unites both hospital and research laboratory in two cities: Manchester and Belfast.
Within discovery science, we are exploring recurrence and metastasis. Manchester scientists are characterising the molecular pathways that regulate tumour-initiating/propagating cells, which are responsible of tumour recurrence, to develop novel therapeutics that tackle the residual disease. Others are working to better understand the mechanism of metastasis in prostate cancer, especially the targeted metastasis towards the bone, and the role of lipid metabolism. GU researchers also have an active interest in the characterisation of new diagnostic and prognostic biomarkers, harnessing expertise in biomedical spectroscopy at the Manchester Institute of Biotechnology.
Translational research is focused on genomics and radiobiology. We have developed hypoxia gene signatures to enable identification of those patients who would benefit from hypoxia-modifying agents prior to radiotherapy. Researchers are also looking at the interplay between hypoxia and DNA repair mechanisms, and how they lead to genetic instability and prostate cancer aggression.
Clinical researchers support biomarker-driven clinical trials of novel treatments for prostate cancer; similar approaches will be implemented for bladder and penile cancers. The aim is to further personalise medicine in this disease site using precise radiotherapy targeting, molecularly targeted drugs and immunotherapy. Within precision radiotherapy, teams are optimising the use of new techniques (MR-linac, proton beam therapy, brachytherapy) and response imaging technology (oxygen-enhanced MRI) to marry the optimal physical and biological targeted therapies for individual patients.
Professor Catharine West explains how her research involving targeting hypoxic tumours, could pave the way to personalise treatment for prostate cancer in “Paving the way for better prostate cancer treatment“, a Cancer Futures article.
Renal cancers are among the most common cancer diagnoses in the UK, with over 13,000 patients being diagnosed each year. Males are more commonly affected, and the commonest histological subtypes include clear cell (75%), papillary (15%) and chromophobe (5%). Many renal cancers are found incidentally, and surgery is the mainstay of treatment for locally confined tumours. For patients who present with stage IV renal cancers, treatments are aimed at trying to control the cancer and maintain quality of life for as long as possible.
There are no proven ‘adjuvant’ therapies which can improve the chances of cure following surgical resection of high-risk renal cell carcinoma (RCC), with multiple negative studies evaluating tyrosine kinase inhibitors (TKIs) in this setting. In patients with metastatic disease (de novo or following disease recurrence), the advent of immunotherapy (IO) combinations has improved median survival to around three years.
First-line treatment options now include single agent oral TKI, TKI + IO combinations, or IO + IO combinations depending on patient histology, prognostic group and co-morbidities. Despite several lines of available therapies, the majority of patients with metastatic renal cancer will still die as a direct result of their cancer diagnosis.
Clinical Research in Manchester
In Manchester, the current Christie RCC research portfolio is focused in 2 main areas:
- Engagement with adjuvant trials of immunotherapy combinations to try and improve the post-operative cure rates for patients with resected high-risk RCC.
- Evaluation of novel treatment options in the 2nd line setting and beyond to ‘rescue’ more patients who fail 1st-line IO combinations.
At The Christie, the team are the top recruiter to the academically funded UK RAMPART trial evaluating the use of adjuvant durvalumab or durvalumab + tremelimumab in comparison to active surveillance following surgical resection. In the metastatic setting, a number of international randomised trials of 2nd/3rd line combination therapies in the post-IO space are currently open to recruitment. Drugs under evaluation include a HIF-2α inhibitor, an anti-LAG-3 antibody, a novel anti-CTLA-4 antibody and drugs targeting myeloid cell populations and the immune micro-environment.
With the Tumour Immunology and Inflammation Monitoring Laboratory (TIIML) laboratory and the University of Manchester Lydia Becker Institute of Immunology and Inflammation, the team has established academic collaborations which have led to the development of two investigator-led studies aimed at improving the efficacy of IO therapy through modulation of the immune micro-environment. The CAPER trial will use oral metronomic cyclophosphamide to try to deplete Treg populations, whilst the LION trial will evaluate the use of celecoxib to decrease tumour promoting inflammation.
In collaboration with digital ECMT and TIIML the ‘proof of concept’ NOTION clinical trial will evaluate home testing of peripheral blood cytokines as an early biomarker of immune-related toxicities and / or treatment response.
The expected aims of the above renal cancer research portfolio include:
- Curing more patients with locally confined RCC through the establishment of effective adjuvant IO therapy. If the trials are positive, then adjuvant IO therapy will become a standard of care approach for all patients with resected high-risk RCC.
- CAPER and LION trials aim to improve the percentage of patients who will benefit from an IO-based treatment approach in the metastatic setting.
- Trials evaluating novel treatment approaches in 2nd/3rd line will hopefully improve the duration of overall disease control for patients with incurable renal cancer. This will allow patients to maintain a better quality of life, whilst also aiming to prolong overall survival by reducing cancer-related deaths.
Where is our research performed?
Prostate, renal and other genitourinary cancer researchers work out of the following facilities in Manchester: