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.
Dr James Kench,
Pathologist5, and Visiting Scientist1.
Dr Kris Rasiah, Head, Academic Urology,
Cancer Research Program1
Associate Professor Susan Clark,
Head, Epigenetics, Cancer Research Program1.
Dr
Vanessa Hayes,
Project Leader, Cancer Genetics, Cancer Research Program1.
Professor C.-Soon Lee, Pathologist6, and Visiting
Scientist1.
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
Peter Duval,
Radiation Oncologist2.
Dr
Raj Javankar,
Radiation Oncologist2.
Dr
Jennifer Turner,
Pathologist2.
Dr
Warick Delprado,
Pathologist7.
Sr
Anne-Maree Haynes,
Clinical Research Co-ordinator1.
Sr
Jayne Matthews,
Clinical Nurse Manager8.
Sr
Louise Hart-Brown,
Clinical Trial Nurse8.
Ms
Ruth PeBenito,
APCC BioResource Node Coordinator1.
Affiliations
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Garvan
Institute of Medical Research, Darlinghurst, Sydney
-
St
Vincent’s Hospital, Darlinghurst, Sydney.
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St
Vincent's Clinic, Darlinghurst, Sydney
-
Sydney
Cancer Centre, Royal Prince Alfred Hospital, Camperdown, Sydney.
-
Institute
of Clinical Pathology and Medical Research, Westmead Hospital,
Westmead, Sydney
-
Royal
Prince Alfred Hospital, Camperdown, Sydney.
-
Douglas
Hanly Moir, Ryde, Sydney.
-
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
over 2,000 prostate cases. The database stores data on over
7,000 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
2006.
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
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
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Affymetrix transcript profiling and bioinformatics
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Protein biomarkers
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Genotype analysis
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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)
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Determinants and outcomes of care for prostate cancer in a whole
population.
2000-2002 $404
000, Department of Veterans’ Affairs: Armstrong B, Smith D,
Rogers J, Grygiel J, Ward J, Berry M.
-
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 transcrip profiling and protein expression profiling.
2002-2004 $320 000, National Health and Medical Research
Council: Henshall S.
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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.
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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.
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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.
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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.
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Infrastructure support for an established cancer
genetics/genomics facility.
2005-2007 $700,000, 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.
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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.
Selected Prostate Cancer Related Publications (last 5 years)
-
Graefen M,
Karakiewicz PI, Cagiannos I, Klein E, Kupelian PA, Quinn DI,
Henshall SM, Grygiel JJ, Sutherland RL, Stricker PD, de Kernion
J, Cangiano T, Schroder FH, Wildhagen MF, Scardino PT and Kattan
MW. Validation study of the accuracy of a postoperative
nomogram for recurrence after radical prostatectomy for
localized prostate cancer. J Clin Oncol 20: 951-956, 2002.
-
Graefen M,
Karakiewicz PI, Cagiannos I, Quinn DI, Henshall SM, Grygiel JJ,
Sutherland RL, Stricker PD, Klein E, Kupelian P, Skinner DG,
Lieskovsky G, Bochner B, Huland H, Hammerer PG, Haese A,
Erbersdobler A, Eastham JA, de Kernion J, Cangiano T, Schroder
FH, Wildhagen MF, van der Kwast T, Scardino PT and Kattan MW.
International validation of a preoperative nomogram for prostate
cancer recurrence after radical prostatectomy. J Clin Oncol
20: 3206-3212, 2002.
-
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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. 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,
2006.
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