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.