Vincent Gnanapragasam
Translational prostate cancer group
Prostate cancer has attracted a huge amount of investment in research and knowledge about this disease is growing exponentially. There is however comparatively little translational research undertaken directly in the clinical disease. The aim of the Translational Prostate Cancer Group (TPCG) is to develop the clinical to laboratory models that will allow more “relevant in man” investigations of prostate cancer in terms of biomarkers, disease progression, response to therapy and novel targets. In essence to use the clinical disease as a model for investigator led hypothesis driven studies. This model can then be used to more rapidly and directly evaluate new markers or drugs. The group works closely with the uro-oncology group in the CRI and is also actively seeking collaboration with interested groups in the Hutchison and wider Cambridge scientific community.
The TPCG is focusing on two areas of laboratory research which is complimented by the development of translational clinical trials at Addenbrookes Hospital.
Role of signalling regulators in prostate cancer growth factor biology
Growth factors are known to be important mediators to tumour growth and progression. In recent years endogenous regulators of growth factor pathways have emerged as potential targets for manipulation. Work in the TPCG is investigating the expression and function of key regulators including Sef and Spred. The goal is to test if these regulators can have clinical application as prognostic biomarkers and therapy targets.
Molecular profiling to determine treatment specific outcome in prostate cancer
Prostate cancer can be effectively treated by different modalities including surgery and radiotherapy. In each modality however there will be those who have a durable good response and those who will not. The ability to predict how a tumour will respond to a particular treatment type would therefore be a powerful tool in clinical decision making. It is currently unknown however if prognostic markers identified in one therapy context are also applicable to other treatments. In this work we are using molecular profiling to identify prognostic markers that can predict clinical outcomes for specific treatments for prostate cancer. The aims 1) To extract mRNA from prostate cancer diagnostic biopsies categorized by different treatments and linked to their long term clinical outcomes. 2) To use this mRNA to test the prognostic significance of known and novel markers in the context of different treatments for prostate cancer.
Clinical-translational research studies
A key aim is to develop the clinical interface for recruiting patients to investigator led clinical trials in prostate cancer. This will be done by setting up research clinics, recruiting patients directly into studies and developing specialised tissue collection to answer research specific questions. The main cohorts of interest in these studies are men treated by androgen deprivation and men with high risk local prostate cancer about to undergo radical surgery. The intention is to develop integrated studies to evaluate new treatments and biomarkers incorporating biological, pathological and imaging assessments. This programme is being undertaken in multi-disciplinary collaboration with the clinical and academic expertise in urology, oncology, pathology and radiology readily available in Cambridge. Current investigator led trials in Cambridge include:
(i) A study of changes in the prostate following androgen deprivation to investigate therapy response and resistance in clinical prostate cancer. Characterisation of in vivo response and resistance in prostate cancer (CHIRRP) 08/H0305/51 Open Nov 2008-current
(ii) Incremental benefit of diffusion weighted MRI using a 3T surface phased array coil versus conventional MRI for the pre-operative assessment of tumour stage in prostate cancer. Diffusion MRI for the Assessment of Prostate tumour Stage (D-MAPS) 10/H0304/54 Start date 1st October 2010
Our laboratory group currently consists of Ajay Joseph, Satoshi Hori and Naveen Kachroo. Funding for our group is from the Royal College of Surgeons of England, the Evelyn Trust, MRC, The Urology Foundation, Addenbrookes Charitable Trust and Cambridge ECMC programme.
Useful links
Department of Urology, Addenbrooke's Hospital- www.camurology.org.uk
CRUK prostate cancer information- http://info.cancerresearchuk.org/cancerstats/types/prostate/
Contact
Click here to contact Dr Vincent Gnanapragasam by email.
Recent Publications
The role of surgery in high-risk localised prostate cancer. Gnanapragasam VJ, Mason MD, Shaw GL, Neal DE. BJU Int. 2011 Sep 27. doi: 10.1111/j.1464-410X.2011.10596.x.
The James Lind Alliance approach to priority setting for prostate cancer research: an integrative methodology based on patient and clinician participation. Lophatananon A, Tyndale-Biscoe S, Malcolm E, Rippon HJ, Holmes K, Firkins LA, Fenton M, Crowe S, Stewart-Brown S, Gnanapragasam VJ, Muir KR. BJU Int. 2011 Oct;108(7):1040-3. doi: 10.1111/j.1464-410X.2011.10609.x.
Laser-capture microdissection and transcriptional profiling in archival FFPE tissue in prostate cancer. Joseph A, Gnanapragasam VJ. Methods Mol Biol. 2011;755:291-300.
Prostate cancer metabolite quantification relative to water in 1H-MRSI in vivo at 3 Tesla. McLean MA, Barrett T, Gnanapragasam VJ, Priest AN, Joubert I, Lomas DJ, Neal DE, Griffiths JR, Sala E. Magn Reson Med. 2011 Apr;65(4):914-9. doi: 10.1002/mrm.22703.
Does a pre-operative urodynamic diagnosis of bladder outflow obstruction improve outcomes from palliative transurethral prostatectomy? Gnanapragasam VJ, Leonard A. Urol Int. 2011 Feb;86(1):85-9.
Expression and functional role of negative signalling regulators in tumour development and progression. Murphy T, Hori S, Sewell J, Gnanapragasam VJ. Int J Cancer. 2010 Dec 1;127(11):2491-9.
Outcomes and predictive factors for biochemical relapse following primary androgen deprivation therapy in men with bone scan negative prostate cancer. Hori S, Jabbar T, Kachroo N, Vasconcelos JC, Robson CN, Gnanapragasam VJ. J Cancer Res Clin Oncol. 2011 Feb;137(2):235-41.
Evidence for distinct alterations in the FGF axis in prostate cancer progression to an aggressive clinical phenotype. Murphy T, Darby S, Mathers ME, Gnanapragasam VJ. J Pathol. 2010 Mar;220(4):452-60.