• About
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The Solid Tumour Group headed by Associate Professor Tim Price began work at The Queen Elizabeth Hospital in 2007 and moved to new laboratories in the Basil Hetzel Institute in 2009. In 2014, the group incorporated the newly established SAHMRI Colorectal Node, and now works on a comprehensive program in colorectal cancer spanning prevention, biology and treatment.

  • Identification, development and clinical trial of new therapeutic agents for the treatment of colorectal cancer
  • Development of new cancer biomarkers of drug resistance and therapeutic targets
  • Further understanding of the molecular mechanisms underlying colorectal cancer
  • Identification of risk factors in groups of under-recognised colorectal cancer patients

We welcome enquiries from students interested in completing research higher degrees or coursework with a research component.

 

Researchers

Students

Dr Dainik Patel is an Oncology fellow who undertakes research with this group.

dainik.patel@sa.gov.au

Molecular Oncology Colorectal Cancer Research Group

Research Projects suitable for Honours and Postgraduate research students

For more information about these projects please contact Dr Jenny Hardingham.
Investigation of circulating DNA mutations in colorectal cancer (CRC)
Circulating tumour-derived DNA (ctDNA) may be present in plasma samples from patients with CRC, and the concentration level has been inversely correlated with survival outcome. It’s thought the ctDNA is derived from circulating tumour cells (CTC) yet there are reports of cases in which ctDNA was detected but no CTC were detectable (Bettegowda et al., 2014), suggesting that tumour DNA could be released from tumour exosomes in the circulation.  ctDNA from plasma (liquid biopsy) provides a means to analyse tumour mutations to enable more sensitive disease monitoring. This means that disease recurrence or progression would be detected at an earlier time-point than would be possible with CT/PET imaging.  CTCs will also be identified in collaboration with Prof Thierry at Uni SA and correlated with ctDNA findings. Techniques include DNA isolation from plasma, digital droplet PCR, mutation or methylation analysis, statistical survival and correlative analyses.
Role of aquaporins 1 and 5 in tumour angiogenesis in colon or breast cancer (2 projects)
Aquaporins (AQPs) are water channel proteins involved in cellular water flux, and implicated in migration, angiogenesis and metastasis in cancer. The drug discovery program in Professor Yool's lab has identified several drugs that modulate aquaporin channel activity. We have found that several of these drugs are effective in vitro at reducing migration and invasion of colon cancer cells and preventing angiogenesis (tumour blood vessel formation). We aim to investigate the efficacy of these drugs in inhibiting angiogenesis in vitro and in halting metastasis in pre-clinical mouse models of human colon or breast cancer. Our hypothesis is that tumour cells that lack AQP1 activity are unable to respond to hypoxia which drives angiogenesis. We will also establish a biobank of organoids cultured from metastatic breast biopsies for research work, in assessing the response to different novel therapeutic drugs in culture, and in characterising the mutational landscape and how that changes with developing resistance.  A biobank of metastatic breast organoids is a much needed resource for future research which is currently lacking in this state. Techniques include cell culture, CRISPR gene knockout, RT-PCR, western blotting, functional assays of cell proliferation, invasion, migration, and angiogenesis and mouse models of human cancer.
Determination of resistance biomarkers in tumour tissue from patients undergoing therapy with anti-VEGF
MicroRNA expression platform will be used in correlative studies on archival tissue to identify biomarkers of resistance to bevacizumab (anti-VEGF monoclonal antibody). Techniques will include DNA and RNA/microRNA isolation from tissue blocks, running microRNA profiles, bioinformatics, and statistical analysis.
SAHMRI Colorectal Node Research Projects

Within the SAHMRI Colorectal Node (based at the BHI), the South Australian Young Onset Colorectal Cancer Study (SAYO) is a hospital-based research program for identifying the causes and consequences of colorectal (bowel) cancer in young adults. The program has an ongoing registry for research participants and an associated database, with topics spanning genetics, pathology, and psychosocial aspects of this condition.  The group consists of a research fellow, medical oncologist and hospital scientist. In addition, a network of collaborators contribute to research directions, analysis and outcomes of the project.

Research Projects suitable for Honours and Postgraduate Students

For more information about these projects please contact Associate Professor Joanne Young.

Early Onset Colorectal Cancer and Metabolic Syndrome

Our preliminary evidence suggests that the increase in incidence of colorectal (bowel) cancer in young adults may be related to the rising rate of metabolic syndrome components in the young adult population. In this study we will explore the overlap of genetic predispositions to both CRC and diabetes in young adults with pre-malignant polyps, or cancer. We will use pedigree analysis, next generation sequencing of the germline, and detailed epigenetic assays of colorectal tissue to identify markers of risk for CRC in the young adult population. It is our long-term objective to help identify at-risk young individuals in primary healthcare settings.

Medical and Psychosocial Aspects of Colorectal Cancer in Young Adults

Colorectal cancer (CRC or bowel cancer) is a common malignancy of older adults. However, over 1100 Australians under the age of 50 develop CRC each year, and the incidence of young onset disease has been rising in Australia and other Western countries during recent decades. Young adults with CRC suffer significant mortality and morbidity in the most productive time of their life. In this project, which would suit a psychology or nursing student, we will undertake a comprehensive study of the medical and psychosocial aspects of having CRC as a young adult. This will include the risk factors such as personal or family history of diabetes, family history of CRC, the diagnostic journey of the patient (since the majority of young patients present late in the course of their disease), and the life impacts post diagnosis on family and relationships, career and education, and physical and mental health.

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

Hardingham JE, Grover P, Winter M, Hewett PJ, Price TJ, Thierry B. Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress. Mol Med; 2015. 21 (Suppl 1): S25-S31.

Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review

Young JP, Win AK, Rosty C, Flight I, Roder D, Young GP, Frank O, Suthers GK, Hewett PJ, Ruszkiewicz A, Hauben E, Adelstein BA, Parry S, Townsend A, Hardingham JE, Price TJ. Rising incidence of early-onset colorectal cancer in Australia over two decades: report and review. J Gastroenterol Hepatol; 2015. 30(1): 6-13.

Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study

Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, Murugappan S, Sidhu R . Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): a randomised, multicentre, open-label, non-inferiority phase 3 study.  Lancet Oncol; 2014. 15(6): 569-79.

Impact of KRAS and BRAF Gene Mutation Status on Outcomes From the Phase III AGITG MAX Trial of Capecitabine Alone or in Combination With Bevacizumab and Mitomycin in Advanced Colorectal Cancer

Price TJ, Hardingham JE, Lee CK, Weickhardt A, Townsend AR, Wrin JW, Chua A, Shivasami A, Cummins MM, Murone C, Tebbutt NC. Impact of KRAS and BRAF Gene Mutation Status on Outcomes From the Phase III AGITG MAX Trial of Capecitabine Alone or in Combination With Bevacizumab and Mitomycin in Advanced Colorectal Cancer. J Clin Oncol; 2011. 29(19): 2675-82.

Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease?

Price TJ, Beeke C, Ullah S, Padbury R, Maddern G, Roder D, Townsend AR, Moore J, Roy A, Tomita Y, Karapetis C. Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease?. Cancer; 2014. 121(6): 830-835.

Funding since 2010

Chief InvesigatorsGranting BodyProject TitleTotal Grant AmountFunding Period
Ramsay R, Worthley D, Heriot A, Narasimhan V, Tie J, Woods S, Price T, Graham T, Hewett P, Grandori CNHMRC (#1156391)From the Stone Age to the State of the Art - Multidimensional Precision Medicine for Peritoneal Colorectal Cancer$1,399,8772019 - 2023
Price T, Holden C, Poprawski D, Roder D, Ratcliffe J, Turnbull D, Buckley E, Singhal N, Wichmann MCancer Council SA Beat CancerDoes ageism prevail in access to multidisciplinary cancer care?$134,7002019
Yool A, Heng S, Hardingham JEAustralian Research Council (DP160104641) Discovery GrantProperties enabling rapid cell migration by aquaporin-1 channel expression$350,000 2016 - 2019
Townsend AR, Hardingham, TJ Price TJ, Gordon L, Lee CCancer Council SA/SAHMRI Beat CancerGenome-wide association study of single nucleotide polymorphisms as predictive biomarkers for sensitivity to anti-EGFR antibody therapy for metastatic colorectal cancer with wild-type RAS$75,0002016
Price TJ, Townsend AR, Hardingham JE (and 20 others)SAHMRI ACRF grant ACRF Innovative Cancer Imaging and Therapeutics Facility $1,800,000awarded November 2013
Price TJ, Hardingham JE, Bruhn M, Townsend AR, Wrin JRoche Australia Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the Phase III AGITG MAX involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer$30,000 2014
Grover PK, Hardingham JE, Cummins ASAHMRI – The Cancer Council of South Australia. (Grant #1029851) Investigation of circulating cancer stem cells in the blood of patients with colon cancer as a cause of secondary spread to the liver$100,000 2012
Townsend AR, Hardingham JE, Price TJ, Tebbutt NSAHMRI – The Cancer Council of South Australia. (Grant #1028595)Impact of the activated EGFR-AKT-mTOR signalling pathway on prognosis and tumour resistance to anti-angiogenic targeted therapy for metastatic colorectal cancer $92,6782012
Hardingham JE, Townsend AR, Price TJOncology research support Scheme A Identification of biomarkers of resistance to bevacizumab therapy.$20,0002011
Townsend AR, Hardingham JE, Price TJAmgenPhase II study of second line therapy with Irinotecan, Panitumumab and Everolimus in metastatic colorectal cancer with KRAS wild type$100,0002009 - 2010
Price TJ et al.Cancer AustraliaPETACC 6 trial, neoadjuvant chemotherapy for T3/T4 rectal carcinoma$475,0002008 - 2010

CollaboratorPositionInstitutionCity Country
Professor Chris O’CallaghanNCIC Clinical Trials GroupTorontoCanada
Associate Professor Geoff LiuOntario Cancer Institute, Princess Margaret HospitalTorontoCanada
Associate Professor Susan ParryNZ Familial GI Cancer Service, Auckland City HospitalAucklandNew Zealand
Associate Professor Niall Tebbutt Austin HealthMelbourneAustralia
Dr Chee K LeeResearch fellowNHMRC Clinical Trials CentreSydneyAustralia
Dr Lavinia GordonBioinformatics, AGRFMelbourneAustralia
Dr Aung Ko Win University of MelbourneMelbourneAustralia
Associate Professor Christophe RostyEnvoi Pathologists BrisbaneAustralia
Professor Andrea YoolHeadPhysiology, School of Medicine, University of AdelaideAdelaideAustralia
Mr P HewettHeadColorectal Surgical Unit, Department of Surgery, The Queen Elizabeth HospitalAdelaideAustralia
Mr David RoddaColorectal Surgical Unit, Department of Surgery, The Queen Elizabeth HospitalAdelaideAustralia
Mr Darren TonkinColorectal Surgical Unit, Department of Surgery, The Queen Elizabeth HospitalAdelaideAustralia
Mr Shanthan GaneshColorectal Surgical Unit, Department of Surgery, The Queen Elizabeth HospitalAdelaideAustralia
Dr Dan WorthleyThe Queen Elizabeth Hospital & University of AdelaideAdelaideAustralia
Dr Ilmars LidumsThe Queen Elizabeth HospitalAdelaideAustralia
Associate Professor Benjamin ThierryIan Wark Research Institute, University of South AustraliaAdelaideAustralia
Associate Professor Andrew RuszkiewiczSA PathologyAdelaideAustralia
Dr Oliver FrankUniversity of AdelaideAdelaideAustralia
Professor David RoderUniversity of South AustraliaAdelaideAustralia
Professor Graeme YoungFlinders UniversityAdelaideAustralia
Dr Ingrid FlightFlinders UniversityAdelaideAustralia
Dr Stephanie WongThe Queen Elizabeth HospitalAdelaideAustralia
Dr Sina VatandoustFlinders Medical CentreAdelaideAustralia
Dr Nicola PoplawskiWomens and Childrens HospitalAdelaideAustralia
Professor Hamish ScottSA PathologyAdelaideAustralia