Prostate and renal cancers are key contributors of cancer related death and morbidity. Early detection and optimal primary treatment improves cure rates and reduces progression to metastasis in both cancer types. Our Clinicians and scientists have developed closely integrated multi-disciplinary research themes including; exploring new markers and imaging for early detection, better modelling of early disease biology, improved methods of risk stratification and novel therapeutic window studies alongside standard clinical treatments. This work is significantly enhanced by our large well annotated bio-repository and high volume urological cancer practice in Addenbrookes.
We are a UK centre for major national and international studies including ProtecT, CANCAP (lead) VoxTox (lead), ICGC (major contributor), PRACTICALS, MOVEMBER, Genomic England, STAMPEDE, RADICALS, PACE, and NIHR IHC. In the last 5 years the prostate research group has together published over 200 papers and initiated 8 translational investigator led studiesThe current research focus in Cambridge is on improving the management and outcomes of men presenting with non-metastatic prostate cancer (over 80% of all diagnosis). To feed into this programme, we have critical strengths in a number of areas:
1. Extensive network of academic research. Cambridge benefits from a vibrant web of cross-collaborative research across the CCC and wider university campus. This encompasses diverse disciplines including pathology, cell and molecular biology, genetics, chemistry, oncology, urology, radiology, epidemiology, engineering, mathematics and computational biology.
2. Excellent clinical care. This is illustrated by the CAMPARI concept, which is a multi-disciplinary group of NHS and academic clinicians as well as allied health professionals with a common goal of improving patient care. This initiative stretches from first presentation, accurate biopsies, precise risk stratification, delivery of state-of-the-art treatment (image guided radiotherapy, robotics, brachytherapy, tailored active surveillance, chemotherapy) as well as excellent patient support. Prostate cancer is strongly associated with age. Collaborative research has identified over 73 single nucleotide polymorphisms (SNPs), or small mistakes in the genetic code, associated with prostate cancer. We are testing how to use these SNPs to identify high risk populations when screening for prostate cancer.
3. Cutting edge imaging. The strength of our integrated imaging capabilities has spread across diagnosis and clinical delivery and into the research arena. This is highlighted by a number of very successful collaborative studies based on MR imaging including the CHIRRP, DMAPS and PAART studies. This is now being extended to new innovative modalities (PET acetate and hyperpolarised C13) with a focus on detecting lethal cancers.
4. Novel diagnostics. Cambridge is also leading in using innovative diagnostics (e.g. introduction of the Uro-Nav biopsy system) and in house development of a novel device for low morbidity, local anaesthetic transperineal biopsies (CAMPROBE). In addition we have established a pipeline of studies exploring new serological assays and biomarkers for detection of lethal cancers working in tandem with image-guided biopsies.
5. Better understanding of disease epidemiology. We have undertaken studies revealing demographic changes in the presentation and treatment of prostate cancer through close working with Public Health England and the cancer registries (assembling cohort data from >20,000 men with longitudinal follow up). More recently this work has resulted in the derivation of a new clinical risk model using data from 10,000 UK men, which outperforms the NICE criteria in predicting cancer specific mortality at diagnosis. Our on-going work will deliver individualised risk prediction and treatment stratification tools through a combination of optimal clinical classification and molecular subtyping .
6. Innovative combinatorial therapies. We have established a platform for window studies to investigate new drug agents in combination with standard therapies. This is exemplified by the currently accruing Astra Zeneca supported CANCAP series of neo-adjuvant studies. In addition, Cambridge leads research in radiotoxicity and technical radiotherapy (VoxTox), which is uncovering new methods to reduce morbidity and side effects for patients.
7. World-class tissue and bio-resource. We have built up (and are continuing to accrue) a large urological bio-repository (Cambridge Urological Bio-repository), which holds tissue (diagnostic and surgical) as well as bio-samples from over 3500 men at different stages and treatments for prostate cancer. All these men have detailed clinical annotation and meticulous follow up. This repository has allowed Cambridge to be a leader in a number of ground-breaking studies, which have elucidated new molecular classifications and predictive markers of outcome.
The Cambridge Renal Cancer Group (CamRenCan) is a collaboration 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. The Centre runs internationally recognised programmes in the genetics of the disease and the metabolic consequences of those genetic abnormalities, in understanding tumour biology and in the treatment of resulting malignancies.
1. Molecular mechanisms of renal cancer progression. Several largescale 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 worldclass 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 wellcharacterised patientdonated 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 and requireIn this work patients with hereditary renal cancer and hence established tumourigenic genetic mutations will be studied (via CCC 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 highrisk 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. 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. tumour biology and in the treatment of resulting malignancies. 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.