Urology 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 Addenbrooke's 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.

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 multi-arm, 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:

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

Links

• Kidney Cancer UK (opens in a new tab)