Our research in the Bladder Cancer Research Centre

Biomarkers and Proteomics

Accurate biomarkers based on the analysis of urine, blood or tumour tissue have the potential to transform the care of patients with bladder cancer by, for example, diagnosing the disease without the need for a cystoscopy (diagnostic biomarkers), better understanding the likely disease course and the risks of recurrence and progression (prognostic biomarkers), or predicting which patients and their tumours will respond to which treatments (predictive biomarkers).

We are interested in all of these possibilities, utilising mass spectrometry for the identification of protein biomarkers and the analysis of exome and transcriptome data for the identification of DNA and RNA biomarkers. Access to large patient cohorts and their associated biospecimens facilitates the validation of promising biomarkers, and the utilisation of in vitro methodologies permits the elucidation of important underlying fundamental biology, with both approaches supporting subsequent translation into the clinic.

Genomics and Bioinformatics

The detailed interrogation of tumour DNA and RNAs by deep sequencing methodologies has allowed us to gain an understanding of the key alterations that drive the development of bladder cancer and subsequent episodes of disease recurrence and progression.

Nevertheless, much work is still needed to understand and integrate a multitude of genomic and epigenomic phenomena, as well as cell biology, immunology and germline genetics. We utilise the latest sequencing approaches to generate datasets for analysis by both existing and novel bioinformatic pipelines and computational biology. Our particular interests include splice variants, circular RNAs, immunotyping, and networks.

Novel Therapeutics

Adjuvant therapies delivered directly into the bladder (intravesical) following transurethral (endoscopic) tumour resection are pillars in the treatment of non-muscle-invasive bladder cancer (NMIBC), and current therapies include mitomycin C and BCG. Although these intravesical treatments have provided moderate efficacy for decades, there remain challenges in the supply of these agents, and they remain toxic with uncomfortable side effects in many patients. Combined with a lack of new intravesical agents coming into the clinic, there remains an unmet need for the identification of new therapies for NMIBC.

Through our close collaboration with The Structural Genomics Consortium at the University of Oxford (Professor Chas Bountra), and utilising our in-house purpose built drug repurposing libraries, we have access to 100s of potentially therapeutic compounds that have never been tested in bladder cancer.

Utilising both 2D and 3D bladder cancer cell culture systems and a wide panel of in vitro assays and ‘omic’ technologies, we have already identified several promising candidates. These studies are ongoing and as we identify promising agents that could be used alongside mitomycin C to improve efficacy, or to potentially be effective alone, we will also identify potential patient stratification opportunities, i.e. identifying drugs that are more effective against specific bladder cancer mutations or molecular subtypes. In parallel, we will be developing companion diagnostics that can be utilised to monitor disease response in patients.

In addition to drug development, through collaboration with the Institute of Immunology and Immunotherapy at the University of Birmingham (Professor Ben Willcox) and the School of Pharmacy and Pharmaceutical Sciences at Cardiff University (Dr Youcef Mehellou), we are working to develop novel immunotherapies that could be synthetic alternatives or replacements for BCG.

As we develop novel therapeutics, we will also work with our clinical trials teams to develop novel clinical trial designs that allow us to rapidly screen our candidate drugs.

Bio-medical Engineering

Cystoscopy underpins the majority of bladder cancer treatment and surveillance and is very much technology-driven. Bio-medical engineering research can thus contribute to the ongoing development of the endoscopes and instruments currently utilised for the management of bladder cancer, as well as lead to innovation across the whole field of bladder cancer - from novel devices to novel drug delivery mechanisms.

We have previously assisted with the development of narrow band imaging (NBI) cystoscopy and TURBT, and continue to work with industry partners to develop new instruments that further facilitate TURBT. Dovetailing with the development of novel instruments and devices to facilitate their design and engineering is the development of accurate bladder and bladder tumour models based upon accurate and detailed analyses of ex vivo tissues.

Clinical Research, Trials and Epidemiology

There is a decades long history of practice-changing clinical research and clinical trials in bladder cancer at the University of Birmingham through the work of Mr Mike Wallace and Professor Nick James. Mr Wallace’s involvement in national studies and Professor James’ leadership of the BC2001 and TUXEDO clinical trials (amongst others) have shaped bladder cancer care internationally. We continue to work very closely with Professor Nick James in his role at The Institute of Cancer Research, London, with collaborations on the BladderPath and RadIO clinical trials, including laboratory-based translational research.

Furthermore, the establishment of the Bladder Cancer Prognosis Programme (BCPP) in 2005 by Professor KK Cheng (alongside Mike Wallace, Nick James, Maurice Zeegers and Rik Bryan) paved the way for a generation of epidemiological and translational bladder cancer research at the University of Birmingham and beyond. The clinical data and biospecimens generously gifted to BCPP by over 1200 bladder cancer patients in the West Midlands represent the strong foundations upon which the BCRC was created. BCPP has done much to progress our knowledge of, and quantify, the relationships between smoking, diet, fluid intake and germline polymorphisms and bladder cancer incidence and outcomes. Originally funded by a Cancer Research UK Population Committee Programme Grant, BCPP has now resulted in >40 publications and has become one of the largest bladder cancer biospecimen collections in the world linked to long-term clinical outcomes. We continue to follow-up the BCPP patients with particular interest in gender disparities in long-term outcomes.

Furthermore, with our collaborators at the University of Maastricht (Professor Maurice Zeegers), we continue to investigate the influence of modifiable exposures on outcomes from bladder cancer. In addition to the clinical links with the Institute of Cancer Research, we will also be closely collaborating with Prof James’s laboratory team in projects investigating the immune architecture of bladder cancer and exploring the role of cancer-associated fibroblasts in treatment resistance.

With our strategic partners in the Cancer Research UK Clinical Trials Unit (CRCTU) at the University of Birmingham we are intrinsically involved with the design and delivery of clinical trials for bladder cancer patients, including SELENIB and BladderPath. Through collaborators at the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU), we have also been very closely involved with the practice changing POUT trial.

Routine healthcare data also represent powerful tools for clinical research and permit the identification of national trends in disease management and outcomes.

Key Strategic Partners

• Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham
• Centre for Medicines Discovery, University of Oxford
• The Translational Oncology and Urology Research Team (TOUR), King’s College London
• University Hospitals Birmingham NHS Foundation Trust
• The Institute of Cancer Research (ICR)