2013 Funded Translational Research Projects

Project: Targeting the mTOR pathway in biliary tract carcinoma

Investigators: Associate Professor John Mariadason (Lead Applicant), Associate Professor Niall Tebbutt, Dr Mehrdad Nikfarjam, Mr Daniel Croagh, Dr Oliver Sieber
Research Organisations: Ludwig Institute for Cancer Research (Lead Organisation), The University of Melbourne, Monash University, Walter and Eliza Hall Institute of Medical Research
Funding: $639,801 over 36 months
Project Description: Biliary tract cancer (cholangiocarcinoma) has a very poor prognosis and is increasing in incidence. There are currently no effective treatments for this disease. We recently completed a clinical trial to assess the activity of a drug called everolimus in biliary tract cancer, and identified a subset of patients who responded to this treatment. This VCA grant application will use cell line models and the tumour samples we collected from patients on this trial to ask why some patients but not others benefit from this treatment. This knowledge will allow us to pre-select patients for further clinical testing of this drug.

Project: The Melbourne Melanoma Project - translating immunology and molecular bio-specimen profiles into the management of melanoma patients

Investigators: Professor Grant McArthur (Lead Applicant), Professor Jonathan Cebon, Professor John Kelly, Mr Paul White, Dr Mark Shackleton, Professor Joseph Trapani, Professor Stephen Fox, Professor Catriona McLean, Associate Professor Alexander Dobrovic, Dr Paul Neeson, Dr David Gyorki, Dr Andrew Haydon, Associate Professor Anthony Papenfuss, Professor Ian Davis, Associate Professor Ben Solomon, Dr Sherene Loi, Dr Campbell Rose, Dr Victoria Mar, Dr Craig Underhill, Dr Tom John, Mr David Speakman
Research Organisations: Peter MacCallum Cancer Centre (Lead Organisation), Ludwig Institute for Cancer Research, Victorian Melanoma Service, Alfred Health, Walter and Eliza Hall Institute of Medical Research, Monash University, Eastern Health  
Funding: $2,975,500 over 36 months
Project Description: There has been unprecedented recent progress in the treatment of melanoma, however much remains to be accomplished. Our proposal boldly aims to reduce the high burden of mortality from melanoma. We will build on our well-established, collaborative and cross-disciplinary network, with engrained communication platforms, to embed our translational research program in routine care of melanoma patients in Victoria. 
We aim to achieve this by:
1) Extending the Melbourne Melanoma Project enrolment to over 2500 participants.
2) Establishing an immuno-oncology translational research laboratory.
3) Supporting clinical trials in melanoma by providing a gene-testing hub for patients enrolled on the Melbourne Melanoma Project.

Project: Solving Unknown Primary CancER (SUPER PLUS): Integrating molecular tests to define site of origin and therapeutically actionable mutations to improve the management of carcinoma of unknown primary

Investigators: Associate Professor Linda Mileshkin (Lead Applicant), Associate Professor Penelope Schofield, Professor David Bowtell, Dr Richard Tothill 
Research Organisation: Peter MacCallum Cancer Centre (Lead Organisation)
Funding: $757,246 over 36 months
Project Description: Carcinoma of Unknown Primary (CUP) are the 6th most common cause of cancer death in Australia and has a dismal prognosis. However, there has been virtually no research into CUP to guide patient management. This project plans to expand and extend our multi-disciplinary program of research into CUP by assessing the value to clinicians and patients of real-time molecular assessment of tumours to determine their likely site-of-origin (primary), as well whether they contain any actionable mutations that would suggest potential benefit from specific targeted therapy. Patients will be enrolled from throughout Victoria including both metropolitan and regional sites.

Project: Victorian Epigenetics Group (VEG): A collaboration for personalised epigenetic cancer therapy through pre-clinical evaluation, novel biomarker development and early phase clinical trials of new drugs

Investigators: Professor Miles Prince (Lead Applicant), Professor Andrew Spencer, Associate Professor Alexander Dobrovic, Dr Nicholas Wong, Professor Ricky Johnstone, Dr Jake Shortt, Professor Andrew Grigg, Professor David Ritchie, Dr Michael Dickinson, Professor David Ashley, Professor Jeffrey Szer, Dr Richard Saffery, Dr Francoise Mechinaud, Dr Melita Kenealy, Dr Mark Dawson
Research Organisations: Peter MacCallum Cancer Centre (Lead Organisation), Alfred Health, Ludwig Institute for Cancer Research, Austin Health, The Royal Melbourne Hospital, Barwon Health, Deakin University, Murdoch Children's Research Institute, Royal Children's Hospital, Cabrini Health
Funding: $2,996,569 over 36 months
Project Description: In every cell in the body there are chemical reactions that switch genes on and off. This gene control mechanism is called epigenetics. We know that cancer can develop or grow because of abnormal chemical (epigenetic) reactions. There are exciting drugs in development that can target epigenetic changes to 're-programme' the rogue cancer cell. This grant brings together internationally recognised epigenetic experts in Victoria to undertake collaborative research. This research will result in clinical trials of 'epigenetic drugs'  for patients with blood cancers incorporating detailed laboratory studies on how these new drugs works and how to use them better.

Project: BH3-mimetics in rational combination therapies to overcome treatment-resistant cancers

Investigators: Professor Andrew Roberts (Lead Applicant), Dr Andrew Wei, Dr Constantime Tam, Professor Geoffrey Lindeman, Professor David Huang, Dr Marco Herold, Professor Andreas Strasser, Professor John Seymour, Dr Kylie Mason, Dr Mark Guthridge
Research Organisations: Walter and Eliza Hall Institute of Medical Research (Lead Organisation), Alfred Hospital, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Australian Centre for Blood Diseases, Monash University
Funding: $2,480,792 over 36 months
Project Description: A major challenge in many cancers is resistance to current treatments. This can occur from the outset of the disease or develop after initially successful therapy. Pioneering research in Victoria has led to the development of a new class of anti-cancer drug - BH3-mimetics. In the laboratory, these drugs show great promise against some therapy resistant cancers, and the first clinical trials confirm this in patients with therapy resistant chronic lymphocytic leukaemia. We now aim to develop rational combination therapies for other resistant cancers, and to conduct clinical trials of these new combinations in patients with leukaemia, lymphoma and breast cancer. 

Project: Enriching cancer clinical trials for patients most likely to benefit from targeted therapies

Investigators: Professor Paul Waring (Lead Applicant), Professor David Bowtell, Dr Jayesh Desai, Associate Professor Clare Scott, Associate Professor Jeremy Shapiro, Professor Danny Rischin
Lead Research Organisation: The University of Melbourne, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research, Cabrini Health
Funding: $1,503,345 over 36 months
Project Description: The success rate of clinical trials is greatly enhanced by enriching patients who are most likely to benefit. We have developed laboratory tests to support five investigator-initiated trials to (i) screen over 1800 Victorians with advanced cancer to recruit 138 patients into three clinical trials (ICECREAM, EVICT, CYCLONE); (ii) measure pharmacodynamic changes in two trials (EVICT, CYCLONE) to determine whether the drugs work in individual patients; (iii) retrospectively interrogate trials (BIOMEASURES, EVICT, ICECREAM) to determine which patients to include in future clinical trials and which patients should not receive approved therapies from which they will derive no benefit.

2013 Workforce Funding Recipients

Dr Jake Shortt

Eva and Les Erdi / Snowdome Foundation Fellowship

Monash Health and Peter MacCallum Cancer Centre

Awakening dormant genes to help the immune system fight blood cancers

Blood cancers switch off normal genes that would normally cause them to die. They also produce signals that camouflage them from the immune system. We are investigating a new drug class that switches normal genes back on in cancer cells. This results in cancer cell suicide and removal of the immune-camouflage, activating the immune system to fight the cancer. We will perform laboratory experiments and follow blood cancer patients receiving this new treatment in a world first clinical trial to monitor its effects on the immune system and help predict who will benefit most.


A/Prof Linda Mileshkin

Victorian Cancer Agency Clinical Research Fellowship

Peter MacCallum Cancer Centre

Clinical Research in Gynaecological cancers and Carcinoma of Unknown Primary (CUP)

The aim of this fellowship is to expand a program of clinical, translational and supportive care research into:

1. Gynaecological Cancer

2. Carcinoma of Unknown Primary

This work will be undertaken from Peter Mac and involve work with multiple collaborators. The Fellowship will allow the researcher to devote most of her time to research as well as continuing to work in a clinical capacity. The capacity for protected time for research will enable the researcher to enhance research productivity, meet research objectives and answer questions to improve the treatment of people affected by cancer.


A/Prof Benjamin Solomon

Victorian Cancer Agency Clinical Research Fellowship

Peter MacCallum Cancer Centre

Molecular therapeutics and biomarkers in Non-small cell lung cancer (NSCLC) and Squamous Cell Carcinoma of the Head and Neck (SCCHN).

Non-small cell lung cancer (NSCLC) and Squamous Cell Carcinoma of the Head and Neck (SCCHN) are major causes of cancer morbidity and mortality in Australia and worldwide. Both malignancies frequently present with locally advanced or metastatic disease and currently available treatments are associated with poor outcomes. The aim of this clinical research fellowship is to conduct clinical trials as well as laboratory-based preclinical and translational studies in order to identify predictive makers and to develop and evaluate new treatments or treatment strategies that will improve outcomes for patients with NSCLC and SCCHN.


Dr George Grigoriadis

Victorian Cancer Agency Clinical Research Fellowship

Monash Institute of Medical Research 

The role of stage specific inflammation/immunomodulation in the evolution of myelodysplastic syndrome from low-to-high risk and impact on therapeutic approaches.

The myelodysplastic syndromes (MDS) are a group of blood cell diseases characterised by anaemia, recurrent infections and bleeding culminating in the development of acute leukaemia. MDS occur principally in older adults with a median age of 70 years with an annual incidence of >20/100,000. An unresolved and important question in MDS is whether survival is improved with drugs that reduce inflammation observed in this disease. The purpose of the study is to understand the role of inflammation at the different stages of the disease and to identify patients with MDS who would potentially benefit from treatment with anti-inflammatory agents.


Dr Sarah Jane Dawson

National Breast Cancer Foundation & Victorian Cancer Agency Clinical Research Fellowship

Peter MacCallum Cancer Centre

Circulating Tumour DNA as a Personalised Biomarker in Breast Cancer 

The measurement of circulating tumour DNA (ctDNA) in the blood of women with breast cancer has the potential to be utilised as a personalised biomarker in disease management. Through recent advances in genomic technologies it is now possible to characterise specific DNA mutations in a patient's tumour and follow these mutations in plasma to accurately measure the amount of ctDNA. This research project will utilise ctDNA to study how breast cancers evolve when they progress and become resistant to treatment. Furthermore, it will evaluate if ctDNA can be used as a form of 'liquid biopsy' to individualise treatment decisions.


Dr Elgene Lim     

National Breast Cancer Foundation & Victorian Cancer Agency Clinical Research Fellowship

Ludwig Institute for Cancer Research

Sensitizing breast cancers to hormone receptor-directed therapies

This project aims to study novel ways to sensitize breast cancer to therapies targeting both oestrogen and androgen receptors in combination with other cancer therapies, utilizing a panel of patient-derived xenografts (PDX) tumours in mice. I will (1) study differences in hormonal signalling in normal breast and breast tumours, (2) establish a panel of well characterized PDX models as a research resource, and (3) evaluate two novel therapeutic strategies not currently in clinical use in PDX models, to provide a strong pre-clinical rationale to translate into early phase clinical trials for patients with hormone receptor positive breast cancer.



Dr Yasmin Jayasinghe

Victorian Cancer Agency Early Career Seed Grant

University of Melbourne

Fertility preservation measures in Victorian children and teenagers with cancer

Reproductive technologies offer the potential for fertility preservation (FP) in cancer survivors through sperm or ovarian tissue retrieval prior to treatment. FP poses unique clinical challenges in the young, however detailed national guidelines do not exist. We aim to 1. Perform an audit of clinical practice at The Royal Children’s and Women’s Hospitals Melbourne to identify barriers to FP; 2. Establish the first paediatric and adolescent FP database with links to national registries; 3. Evaluate a FP toolkit delivering information to clinicians and families; 4. Establish the first Paediatric and Adolescent FP guidelines in Victoria


Dr Mitchell Lawrence

Victorian Cancer Agency Early Career Seed Grant

Monash University

Modelling the variability of localised human prostate cancer within each patient

Most men with localised prostate cancer have multiple distinct tumours within their prostate. The characteristics of these tumours can vary greatly. This variability makes it challenging to predict which tumours may be aggressive. For some patients, this complicates the decision about the most appropriate treatment to balance possible side-effects with the risk of disease progression. The goal of this study is to collect and compare separate tumours from individual patients. This will reveal the degree of functional differences between tumours and help clinicians and scientists determine which tumours are clinically relevant.


Dr Robert O'Donoghue

Victorian Cancer Agency Early Career Seed Grant

The Walter and Eliza Hall Institute of Medical Research

Investigating IL-6/11 as Therapeutic Targets for the Treatment of Lung Cancer

Lung cancer is the leading cause of cancer related death and fourth leading cause of death in Australia. While targeted therapies are available to a minority of lung cancer patients, no current treatments for lung cancer have been successful in prolonging life. My preliminary data shows in a mouse model of lung cancer the cytokines interleukin-6 and interleukin-11 promote lung cancer development and progression. These exciting results implicate IL-6 and IL-11 as molecules that underpin the progression of lung cancer, and this project will investigate the potential of anti-IL-6 /11 therapies for the treatment of human lung cancer.


Dr Bhupinder Pal

Victorian Cancer Agency Early Career Seed Grant

The Walter and Eliza Hall Institute of Medical Research

Harnessing genomic studies to identify novel biomarkers for breast cancer diagnosis and therapy

We have generated a panel of patient-derived tumours that include aggressive basal-like and luminal B breast cancer. These recapitulate the primary tumour and are being used to test novel targeted therapies. The aim of this project is use state-of-the-art genomic tools (whole exome and RNA sequencing) to identify perturbed molecular pathways to identify ‘Achilles heel’ mutations and inform our pre-clinical models. We will also perform single cell gene profiling of pre-malignant stem and progenitor (‘daughter’) cells from BRCA1 and BRCA2 breast tissue to delineate molecular changes that could be exploited in diagnosis and therapy.


Dr Hang Quach

Victorian Cancer Agency Early Career Seed Grant

St. Vincent's Hospital

Mechanisms of immune suppression and drug resistance in multiple myeloma via GRP78 upregulation, and the therapeutic effect of suppressing GRP78 selectively within the myeloma microenvironment.

Multiple myeloma is an incurable blood cancer. It causes bone-marrow failure, immune deficiency, and morbidity from multiple end-organ damages. Relapse after treatment is inevitable from drug-resistance and failure of the host immune system to eradicate residual myeloma-cells. This project studies how myeloma-cells avoid immune destruction and how drug-resistance develops. We will explore the contribution of a key cellular-protein GRP78 via mouse models and correlate findings with human disease by studying bone-marrow biopsies from patients. We will test the feasibility of a novel therapeutic that will block GRP78 selectively in plasma-cells.


Dr Jian zhong (Bill) Tang

National Breast Cancer Foundation & Victorian Cancer Agency Early Career Seed Grant

Peter MacCallum Cancer Centre

Identify genetic drivers of metastasis and therapy resistance in melanoma by transposon mutagenesis screens

Melanoma, a dangerous cancer usually developing in skin, is very common in Victoria and Australia, particularly affecting young people. Once melanoma spreads, it is usually incurable. Although new treatments have recently offered hope, the benefit offered by these is usually not durable as drug resistance develops in most cases, often after only a few months. By using cutting-edge technologies, my research seeks to discover how melanoma spreads and becomes resistant to drugs. As such, its ultimate goal is to uncover new approaches to preventing the spread and improving the treatment of melanoma, with potential benefits for other cancers too.


Dr Jeanne Tie

Victorian Cancer Agency Early Career Seed Grant

The Walter and Eliza Hall Institute of Medical Research

Circulating Cancer DNA as a Blood Biomarker of Prognosis and of Chemotherapy Benefit in Patients with Advanced Colorectal Cancer

Tests that improve our ability to personalise treatment for patients with colorectal cancer, by guiding initial treatment decisions and accurately assessing treatment effectiveness, are urgently needed. The proposed research builds on our initial study of circulating tumour DNA suggesting this accurately predicts patient prognosis, and improves the measurement of treatment benefit. This test can potentially provide an earlier and more accurate measure of treatment benefit. In this study we will collect blood samples from patients undergoing treatment for advanced colorectal cancer to validate and extend the findings from our initial study.


Dr Aung Ko Win

Victorian Cancer Agency Early Career Seed Grant

University of Melbourne

Can we predict who will get a second bowel tumour?

Even after having their cancer surgically removed, bowel cancer patients are still at risk of having a second bowel cancer. The risks are likely to vary from patient to patient but at present almost nothing is known on how to predict who is most likely to get a second cancer and therefore who should have most surveillance. Using the 15-years follow-up data from an international study of over 11,000 bowel cancer cases, we will identify how personal characteristics, family history of cancer, and features of the first bowel cancer predict risk of second bowel cancer.


Ms Lucy Forrest,

Palliative Care Research Network Victoria PhD Research Scholarship

University of Melbourne, Mercy Palliative Care

This grant is for research examining the experience of music and music therapy for paediatric palliative care patients and their parents, who come from diverse cultural backgrounds. The study aims to develop understanding of how families who are caring for a child in home-based paediatric palliative care are engaging with palliative care and specifically music therapy.


Dr Daniel Gough

Monash Comprehensive Cancer Consortium Early Career Seed Grant

Centre for Cancer Research, Monash Institute of Medical Research

This grant is for research on medulloblastoma – the most common malignant childhood brain tumour.


A/Prof Andrew Wei

Monash Partners Academic Health Science Centre Clinician Researcher Fellowship

Australian Centre for Blood Diseases, the Alfred Hospital

This grant is for developing the Alfred Centre for Acute Myeloid Leukaemia research within the Monash Partners Academic Health Science Centre


Dr Sue Evans

Monash Partners Academic Health Science Centre Clinician Researcher Fellowship

Monash University

This grant is for assessing the value of clinical cancer registries and identifying how registries could be enhanced to provide optimal value to clinicians, hospitals, consumers, government, and industry.


Dr Tom John

Cancer Council Victoria Mesothelioma Grant

Ludwig Institute for Cancer Research

This grant is for exploring a range of molecules in mesothelioma to determine if they are clinically useful. Furthermore it will aim to collect fresh tissue prospectively so that novel markers can be investigated, which may lead to the identification of clinically relevant markers.