Prostate Cancer Research Group
Professor Christopher Hovens
Location: Room 515/ Level 5, Clinical Sciences Building, Department of Surgery, RMH
Prostate cancer in the Western world represents a continuing clinical paradox. The prostate is the most cancer-prone internal organ based on cancer incidence rates (1), yet only an unpredictable 10% of prostate cancer cases progress to lethality. Similar to most other solid tumours, nearly all lethal cases segregate with metastasis and subsequent emergence of therapy-resistant disease. Large-scale genomic analyses have been reported for primary localised prostate cancer (1, 2, 3, 4) as well as for metastatic end-stage cancers (5, 6, 7). However, these studies have been restricted to reporting the most prevalent somatic aberrations associated with the dominant clone of the tumour without permitting an analysis of subclonal complexity or how this complexity impinges on metastatic potential and resistance to treatment. More recent studies have highlighted the potential of deep genomic analysis and multi region sequencing of primary tumours from small cohorts of patients for exploring the nature of intratumour heterogeneity, and for discovering genomic processes linked with cancer evolution (10, 11). However, to identify the origins of candidate subclones contributing to metastasis and decrypt drivers of tumour subclonal expansion, in-depth longitudinal genomic studies are required (10).
To this end we have performed deep genomic analysis of matching primary and metastatic prostate tumours from a small, unique cohort of patients, revealing for the first time, the precise patterns and direction of lethal metastatic spread as well as determined the tumour subclonal complexity at primary and metastatic sites. By ultra-deep sequencing of end-stage blood we have detected both metastatic and primary tumour clones, even years after removal of the original prostate. Analysis of mutations specifically associated with metastasis has revealed an enrichment of TP53 missense mutations, and additional sequencing of metastases from an independent cohort has demonstrated that the late acquisition of TP53 mutations in primary tumour subclones is linked with expansion of subclones with metastatic potential which can be detected in the blood.
Professor Christopher Hovens, Principal Research Fellow,
Dr Niall Corcoran, Research Fellow,
Dr Michael Clarkson, PhD - Post Doc
Miss Natalie Kurganovs, BBioMed (Hons) - PhD student
Mr Patrick McCoy, BSc (Hons) - PhD student
Mr Marek Cmero, BCS/BComm (Bachelor of Computer Science/Bachelor of Commerce) from UWA and MSc (Bioinformatics) at University of Melbourne, PhD student
Dr Ken Chow, MBBS - PhD Student
Mr Scott Peng, BBiomed - Hons Student
Miss Nadia Tolich, BBiomed - Medical Student
Mr Ryan Stuchbery, Senior Research Assistant, BSc (Hons)
Ms Anne Nguyen, Research Assistant, BSc (Hons)
Professor Hovens has built up an extensive collaborative network which includes researchers from AGRF, VLSCI, NICTA, Translational Pathology at the University of Melbourne, The University of Cambridge, the Prostate Cancer TCGA and the Sanger Centre UK.
Professor Hovens received $7.5m from the Federal Government with Professor Anthony Costello (Department of Urology, RMH) in 2008 to establish a Research Centre for Prostate Cancer (Australian Prostate Cancer Research Centre (APCRC) at the Epworth Hospital). Funding for this Centre has been extended until 2018 at $1.5m per year. In 2008, he received a project grant ($460 000) from the Prostate Cancer Foundation of Australia for Circulating Cells as Biomarkers for Prostate Cancer study. His research laboratory has received a sponsored research program with Velacor Therapeutics through which he has a research contract for $220,000 for preclinical optimisation of Vel015. In 2007, he received $330 000 NHMRC Development grant to study Vel015 as a novel therapeutic for brain tumours. He has also received research funding from the Victorian Prostate Cancer Research Consortium (VPCRC, $230 000), Urology Trust ($150,000), and the Prostate Cancer Foundation Australia (PCFA, $230,000). He is a either CIA or CIB on three current NHMRC project grants with combined funding of over $1.5m. Spin Out companies he has co-founded, which are still active, have raised to date over $6.5m.
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For further information about this research, please contact Professor Christopher Hovens