Research

Research and development in the department of urology in Cambridge

The urology department in Cambridge is involved in a wide range of academic activity. The clinical department is involved in regular audit of practice and in commercial and NCRN portfolio studies. In addition to this there are programmes in academic, undergraduate and postgraduate teaching. 

Research and development committee

The departmental urology research and development committee meet quarterly chaired by Mr VJ Gnanapragasam and is the point of contact for potential new studies. The committee reviews the department’s trials and studies portfolio and any issues on recruitment and resources. Trials work is supported by a dedicated urology research nurse. Enquiries about potential trial and studies can be sent to Mr VJ Gnanapragasam (email vjg29@cam.ac.uk or Mrs S Taylor (email stephanie.taylor@addenbrookes.nhs.uk). A list of current trials is listed below. In addition to uro-oncology (see below) there are research programmes in benign urological conditions with specific departmental interests in benign bladder and prostatic conditions (Mr N Thiruchelvam), stone disease (Mr OJ Wiseman) and urology service configuration and delivery (Mr C Kastner).

List of current commercial and NCRN portfolio studies in the department

  • Prostate and bladder cancer – Urosense 
  • Bladder dysfunction and incontinence – ANTIC, MASTER, ALTAR, PROSPUR, LEADERSHIP 301, PLUS
  • Urethral stricture disease – OPEN
  • Stone disease – Stent trial
  • Artifical urinary sphincter trials – RELIEF II, SATURN

Academic teaching programme

The urology department has an active academic programme with a monthly afternoon meeting following the audit and business meeting. This is led by the consultants and covers a range of urological topics in a rolling rota. These sessions are designed to provide updates and new developments in providing state of the art urological care. Sessions include presentations by consultants, registrars and invited speakers. There is also an annual, session where departmental audits and studies are presented. This is co-ordinated by Mr Wiseman.

Academic Urology Group (AUG), Department of Surgery

The main focus of AUG (http://surgery.medschl.cam.ac.uk/divisions-and-groups/academic-urology-group/) is in prostate and renal cancer research which are major components of the CRUK Cambridge Centre as the Urological Malignancies Theme (https://crukcambridgecentre.org.uk/research/programmes/urological-malignancies). However this are also developing strands of bladder cancer research and non-cancer clinical trials. Renal, bladder and prostate cancer patients are asked to participate in the 100,000 genome project (GEL; https://www.genomicsengland.co.uk/the-100000-genomes-project/), these tumour types are leading recruitment to this important study at University of Cambridge. The group is led by  Vincent Gnanapragasam (University Lecturer) for prostate cancer and urology biorepository (DIAMOND), and Grant Stewart for renal cancer (lead for the Cambridge Renal Cancer collaborative (CamRenCan) as well as 2 clinical lecturers (Tom Mitchell and Satoshi Hori). The unit is an accredited training centre for academic clinical fellows with regular intakes every year. At the current time there are 6 ACF in the department.

Prostate cancer research

The prostate cancer programme in Cambridge covers basic, translation and clinical research. A principle focus is on castrate refractory prostate cancer and improving primary therapy for high risk disease. Professor Neal is the PI for a number of national prostate cancer studies including the PROTECT and PROMPT programmes. He also leads a translational science group in the Cambridge Research Institute with a focus on androgen receptor signalling, metabolism and novel diagnostic biomarkers. Vincent Gnanapragasam is the PI for a number of investigator led window trials in prostate cancer including the CHIRRP and DMAPS study and conducts laboratory research in growth factor signal regulation and translational research in treatment specific predictive biomarkers.

The prostate cancer research programme in Addenbrookes includes the collection of pre and post therapy biological samples (tissue, blood and urine) from men having different treatments for prostate cancer with further samples collected in follow up. These samples are used in multi-platform genomic analysis using high throughout and next generating sequencing methods to identify novel biomarkers. This work is underpinned by focused clinically relevant biological studies in cell lines, animal models and human tissue samples. A key aspect is close collaboration with other scientists and academics in Cambridge as well as nationally and internationally to optimally exploit skills and knowledge across different disciplines.

Working closely with urology colleagues we are also developing and assessing optimal pathways for clinical diagnosis and management including active surveillance protocols. A further important area is in seeking to improve the therapy pathways of patients by using novel biopsy and imaging methods to better diagnosis and monitor treatment outcomes. To achieve this we have established key clinical collaborations with a multi-disciplinary team including pathology, radiology and oncology. This is allowing us to develop novel translational window trials of new drugs and therapies in prostate cancer as well as clinical trials to test optimal therapy in different patient groups. These studies include biological and imaging endpoints as potential early surrogates of therapeutic efficacy.

 

Renal cancer research

The Cambridge Renal Cancer collaboration (CamRenCan) is a group of basic and translational scientists together with clinicians working synergistically towards the common goal of improving outcomes of patients with renal cancer via multimodal research strategies.

CamRenCan has 3 main research strands:

  1. Molecular mechanisms of renal cancer progression. Several large­-scale resequencing efforts have characterized the genomic landscapes of renal cancer. Unlike in many other cancer types, however, few actionable genetic alterations have been identified. Experimental approaches are thus needed for a better understanding of the molecular mechanisms of renal cancer progression. CamRenCan harbours several world­-class research groups that focus on functional analysis of renal cancer in a wide range of model systems and experimental areas, such as metabolomics, functional genetics, drug development and stem cell biology. This work is intimately linked with the analysis of clinical renal cancer cohorts, for which genetically and pathologically well­-characterised patient­-donated cancer tissue with high fidelity clinical information is essential. We are also continuously developing new renal cancer models for functional biology. The aim of this work is to identify novel molecular dependencies in renal cancer for further translational development.
  2. Identification of kidney cancer at a curable stage. We seek to improve identification of patients with curable, early stage renal cancer before this progresses to lethal disease. A key aspect of this approach is the improved delineation of which small renal masses are malignant rather than benign (~30% cases), this is currently challenging on standard imaging approaches and hence many patients are exposed to potentially unnecessary surgery. Furthermore, we need to better understand which small renal cancers have the potential for rapid progression. In this work, patients with hereditary renal cancer and hence established tumourigenic genetic mutations will be studied (via medical and surgical renal genetics clinics) together with those patients with sporadic disease. Using experimental radiology, circulating tumour DNA, metabolomics and cell of origin studies these lesions will be better delineated than is currently possible, leading to a rapid improvement in patient care.
  3. Optimal management of patients with high risk initially localised renal cancers. In this theme of work, we aim to improve identification of the patients with high-risk renal cancer who will relapse after nephrectomy for whom there are currently limited curative treatment options available. We seek to identify the therapies to which such patients would benefit from. Successful adjuvant treatment of RCC would make a substantial impact on the burden of the disease. No adjuvant therapy has been proven to date and trials take a decade or more from concept to result. It is therefore a priority for the CamRenCan to consider ways to accelerate progress in adjuvant trials. CamRenCan is working with the MRC to develop a multiarm, multistage design to maximise clinical trial design efficiency (RAMPART). This study together with others being developed from within CamRenCan form the backbone to this theme. Using blood, urine, stool and tissue samples donated by patients in these trials we will be well placed to develop predictive assays of response and identification of residual or recurrent disease.

List of current active academic renal and bladder cancer studies

  1. Tissue surplus to diagnostic requirements is being banked for molecular & genetic studies of urological malignancy
  2. Renal tissue microarray for biomarker detection and profiling
  3. NEOSUN and SORCE
  4. NAXIVA

Links

Kidney Cancer UK: https://www.kcuk.org.uk

 

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