St. Vincent's Hospital Campus Prostate Cancer Group (SVCPCG)

Chief Investigators

Associate Professor Susan Henshall, Head, Prostate Cancer Group, Cancer Research Program1
Professor Rob Sutherland, Director, Cancer Research Program1
Associate Professor John Grygiel, Medical Oncologist2
Associate Professor Phillip Stricker, Director, Uro-Oncology Research3
Dr Lisa Horvath, Medical Oncologist4, and Visiting Scientist1
Associate Professor James Kench, Pathologist5, and Visiting Scientist1
Dr Kris Rasiah, Head, Academic Urology, Cancer Research Program1
Professor Susan Clark, Head, Epigenetics, Cancer Research Program1
Dr David Golovsky, Urologist2
Dr Phillip Brenner, Urologist2
Dr Gordon O’Neill, Urologist2
Dr Raji Kooner, Urologist2
Dr David Ende, Urologist2
Dr David Dalley, Medical Oncologist2
Dr Raj Javankar, Radiation Oncologist2
Dr Jennifer Turner, Pathologist2
Dr Warick Delprado, Pathologist6
Sr Anne-Maree Haynes, Clinical Research Coordinator1
Sr Jayne Matthews, Clinical Nurse Manager7
Ms Ruth PeBenito, APCC BioResource Node Coordinator1

Affiliations

1. Garvan Institute of Medical Research, Darlinghurst, Sydney
2. St Vincent’s Hospital, Darlinghurst, Sydney.
3. St Vincent's Clinic, Darlinghurst, Sydney
4. Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, Sydney.
5. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, Sydney
6. Douglas Hanly Moir, Ryde, Sydney.
7. Prostate Cancer Centre, St Vincent’s Clinic, Darlinghurst, Sydney.

Tissue Bank

The SVCPCG developed an extensive prostate tissue bank and clinical database prior to the establishment of the APCC BioResource. The tissue bank houses tissue, both fresh and paraffin-embedded from approximately 3,000 prostate cases. The database stores data on over 9,000 prostate cases, containing extensive clinical and pathological outcome data compiled from sources including prospective collection at clinical review, direct patient survey and retrospective collection from the State Cancer Registry. The tissue bank and database cover prostate cases that were treated on the St Vincent’s Hospital campus between 1986 and 2008.

Research Activity

The SVCPCG, based at St Vincent's Hospital and Clinic and the Garvan Institute of Medical Research, is a close collaboration of research scientists and clinicians that are involved in projects of tumour biomarkers, genotypic markers of prostate cancer risk, therapeutic response and outcome and clinical trials of novel therapeutics in prostate cancer. These clinical goals are underpinned by an active basic research program aimed at the identification and functional characterisation of molecules pivotal to the development and progression of prostate cancer.

A major focus of the group is to identify and characterise novel predictors of prostate cancer outcome. There are a considerable number of publications assessing the ability of biomarkers to predict an earlier time to relapse of prostate cancer following radical prostatectomy. Despite these data, there remain no molecular markers of routine clinical utility which differentiate localised prostate cancers with an aggressive phenotype, and clinicians still rely on conventional preoperative and postoperative prognostic indicators such as pretreatment PSA levels, pathological stage and Gleason grade in routine decision-making. This reflects most likely the fact that studies that have correlated differences in gene expression with patient outcome have assessed candidate genes with limited predictive power that provide no additional prognostic information above the conventional variables, and accentuates the need to discover novel genes with strong predictive ability. A significant achievement for this group has been the ability to conduct multi-centre trials of biomarkers in NSW. The trial of AZGP1 as a marker of metastatic prostate cancer in 4 teaching hospitals in Sydney is not only the first of its kind in Australia but is the first time that a co-ordinated approach to prostate cancer translational research has been supported over several clinical sites outside treatment trials.

A new direction for this group is to identify predictive markers of chemosensitivity in advanced prostate cancer. Recently, docetaxel-based chemotherapy has been demonstrated to confer a survival advantage in patients with hormone-refractory prostate cancer. Unfortunately, only 50% of men respond to such treatment but docetaxel causes significant toxicity. Predictive biomarkers could identify patients likely to respond to treatment, thereby also decreasing the morbidity for those who are not likely to respond.

Areas of Expertise

• Affymetrix transcript profiling and bioinformatics

• Protein biomarkers

• Genotype analysis

• Epigenetic analysis

• Clinical trials of novel biomarkers

• Molecular biology, in particular functional analysis of molecular markers and/or targets

Major Prostate Cancer Related Grants (last 5 years)

Steroid and growth factor signalling in the pathophysiology of breast and prostate cancer. 2000-2004 $1.995 million, The Cancer Council NSW: Sutherland RL, Daly R, Musgrove E, Ormandy C, Watts C.

Characterisation of the prostate androgen-response program using combined transcript profiling and protein expression profiling. 2002-2004 $320 000, National Health and Medical Research Council: Henshall S.

Investigation of the role of the Wnt signaling pathway in prostate cancer: Is Secreted Frizzled-related Protein 4 an inhibitor of prostate cancer growth? 2004-2005 $US98 000, US Congressional-directed medical research program: Horvath L.

Control of cell proliferation and differentiation in breast and prostate cancer. 2004-2008 $4.74 million, National Health and Medical Research Council: Sutherland RL, Daly R, Musgrove E, Ormandy C.

Examining genes that are associated with a high risk of developing breast and prostate cancer in order to develop better detection and management strategies. 2005-2007 $592 800, Cancer Institute NSW: Hayes V.

Research to delineate markers of outcome and novel therapeutic targets for improved prostate cancer prognosis and treatment. 2005-2007 $592 800, Cancer Institute NSW: Henshall S.

Infrastructure support for an established cancer genetics/genomics facility. 2005-2009 $1.446M, Cancer Institute NSW: Hayes V, Ormandy C, Breit S, Butt A, Clark S, Daly R, Grygiel J, Henshall S, Horvath L, Kaplan W, Kench J, Kohonen-Corish M, Musgrove E, O’Brien P, Russell P, Sutherland R, Ward R.

Identification and validation of molecular markers of prognosis and therapeutic responsiveness in prostate cancer. 2005-2009 $3.75 million, Cancer Institute NSW: Clark S, Henshall S, Russell P, Horvath L, Sutherland R, Kench J, Lee CS, Molloy P, Grygiel J, Stricker P, Boyer M.

Image Analyser for tissue pathology research. 2006 $278 496. Cancer Institute NSW: Henshall S, Horvath L, Murphy N, Biankin A, O’Brien P, Kohonen-Corish M, Clarke S, Millar E, Graham P, Hamilton A, McBride J.

Confirming the use of a marker in prostate tissue to facilitate earlier intervention and more customized treatment of prostate cancer. 2007-2008 $50,000. EJ Whitten Foundation: Henshall S.

Identification of plasma biomarkers of chemotherapy resistance in hormone-refractory prostate cancer. 2007-2008 $50,000. Hillcrest Foundation: Henshall S.

Selected Prostate Cancer Related Publications (last 5 years)

Welsh JB, Sapinoso LM, Kern SG, Brown DA, Liu T, Bauskin AR, Ward RL, Hawkins NJ, Quinn DI, Russell PJ, Sutherland RL, Breit SN, Moskaluk CA, Frierson Jr HF and Hampton GM. Large scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proc. Natl Acad. Sci. USA 100: 3410-3415, 2003.

Henshall SM, Afar DEH, Hiller J, Horvath LG, Quinn DI, Rasiah KK, Gish K, Willhite D, Kench JG, Gardiner-Garden M, Stricker PD, Sher HI, Grygiel JJ, Agus DB, Mack DH and Sutherland RL. Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res 63: 4196-4203, 2003.

Henshall SM, Afar DE, Rasiah KK, Horvath LG, Gish K, Head DR, Caras I, Ramakrishnan V, Wong M, Jeffry U, Kench JG, Quinn DI, Turner JJ, Depardo W, Lee CS, Golovsky D, Brenner PC, O’Neill GF, Kooner R, Stricker PD, Grygiel JJ, Mack DH, Sutherland RL. Expression of the zinc transporter ZnT4 is decreased in the progression from early prostate disease to invasive prostate cancer. Oncogene 22: 6005-6012, 2003.

Bhaskar V, Law DA, Ibsen E, Breinberg D, Cass KM, DuBridge RB, Evangelista F, Henshall SM, Hevezi P, Miller JC, Pong M, Powers R, Senter P, Stockett D, Sutherland RL, von Freeden-Jeffry U, Willhite D, Murray R, Afar DE, Ramakrishnan V. E-selectin up-regulation allows for targeted drug delivery in prostate cancer. Cancer Res 63:6387-94, 2003.

Horvath LG, Henshall SM, Kench JG, Saunders DN, Lee CS, Golovsky D, Brenner PC, O’Neill GF, Kooner R, Stricker PD, Grygiel JJ, Sutherland RL. Membranous secreted frizzled-related protein 4 predicts for good prognosis in localized prostate cancer and inhibits PC-3 cellular proliferation in vitro. Clin Cancer Res, 10: 615-625, 2004.

Afar DE, Bhaskar V, Ibsen E, Breinberg D, Henshall SM, Kench JG, Drobnjak M, Powers R, Wong M, Evangelista F, O'Hara C, Powers D, DuBridge RB, Caras I, Winter R, Anderson T, Solvason N, Stricker PD, Cordon-Cardo C, Scher HI, Grygiel JJ, Sutherland RL, Murray R, Ramakrishnan V, Law DA. Preclinical validation of anti-TMEFF2-auristatin E-conjugated antibodies in the treatment of prostate cancer. Mol Cancer Ther 3:921-32, 2004.

Horvath LG, Henshall SM, Lee CS, Kench JG, Golovsky D, Brenner PC, O’Neill GF, Kooner R, Stricker PD, Grygiel JJ, Sutherland RL. Lower levels of nuclear beta-catenin predict for a poorer prognosis in localized prostate cancer. Int J Cancer 113: 415-22, 2005.

Bauskin AR, Brown DA, Junankar S, Rasiah KK, Eggleton S, Hunter M, Liu T, Smith D, Kuffner T, Pankhurst GJ, Johnen H, Russell PJ, Barret W, Stricker PD, Grygiel JJ, Kench JG, Henshall SM, Sutherland RL, Breit SN. The propeptide mediates formation of stromal stores of PROMIC-1: role in determining prostate cancer outcome. Cancer Res 65: 2330-2336, 2005.

Rasiah KK, Kench JG, Gardiner-Garden M, Horvath LG, Biankin AV, Golovsky D, Brenner PC, Kooner R, O'Neill GF, Turner JJ, Delprado W, Lee C-S, Brown DA, Breit SN, Grygiel JJ, Stricker PD, Sutherland RL and Henshall SM. (2006). Aberrant expression of neuropeptide Y and macrophage inhibitory cytokine-1 are associated with premalignant prostate disease and prostate cancer progression after radical prostatectomy. Cancer Epidemiology, Biomarkers & Prevention. 15, 711-6.

Henshall SM, Horvath LG, Quinn DI, Eggleton SA, Grygiel JJ, Stricker PD, Biankin AV, Kench JG and Sutherland RL (2006). Zinc-alpha2-glycoprotein expression as a predictor of metastatic prostate cancer following radical prostatectomy. J Natl Cancer Inst 98: 1420-1424.

Horvath LG, Lelliott JE, Kench JG, Lee CS, Williams ED, Saunders DN, Grygiel JJ, Sutherland RL and Henshall SM (2007). Secreted frizzled-related protein 4 inhibits proliferation and metastatic potential in prostate cancer. Prostate 67: 1081-90.

Ho LL, Kench JG, Handelsman DJ, Scheffer GL, Stricker PD, Grygiel JG, Sutherland RL, Henshall SM, Allen JD and Horvath LG (2008). Androgen regulation of multidrug resistance-associated protein 4 (MRP4/ABCC4) in prostate cancer. Prostate: 10.1002/pros.20809.