2019 Project Grants
Project: CaPP3 Australia: A randomised double blind dose non-inferiority trial of aspirin in Lynch syndrome with open label extension. (CaPP3 Australia)
Investigators: Prof Finlay Macrae (Lead Applicant), Prof Ingrid Winship, Prof Allan Spigelman, Prof John Burn, Dr Jenni Jenkins, A/Prof Judy Kirk, Prof Rodney Scott, and Mr Mark Dunstan
Collaborating Organisations: Melbourne Health, Peter MacCallum Cancer Centre, St Vincent's Hospital Sydney, Westmead Hospital, Royal Brisbane and Womens Hospital
Funding: $299,260 over two years
Project Description: Lynch syndrome (LS) is an inherited disorder that increases the risk of cancer, particularly cancers of the bowel. The CAPP2 randomised trial of 600mg aspirin vs placebo showed, amongst other evidence, that aspirin prevents cancer. However, lower doses may also be effective, with less side effects. This is CaPP3: a randomised dose evaluation trial in LS, assessing 600mg, 300mg or 100mg doses of aspirin (no placebo). This application is to fund longer term arms of the CaPP3 trial to increase precision in determining if lower doses are as effective. CaPP3 addresses arguably the most important cancer prevention question at hand.
Project: Piloting a model of universal self collection for cervical screening in primary care in Victoria: The solution to a decade of declining participation and to longstanding inequity?
Investigators: Prof Margaret Kelaher (Lead Applicant), A/Prof Julia Brotherton, Dr Claire Nightingale, Prof Marion Saville, Dr Lara Roeske, A/Prof David Hawkes, and Prof Karen Canfell
Collaborating Organisations: University of Melbourne and VCS Foundation
Funding: $297,953 over two years
Project Description: Australia’s renewed national cervical screening program, in which human papillomavirus (HPV) testing replaced cytology-based screening, also enabled a HPV self-collection pathway for women who were under-screened. This pathway aimed to reduce inequities within the program. Data collected from early adopters of this pathway indicates it is highly acceptable to women and their practitioners. There are, however, limitations in its implementation, largely associated with the strict eligibility criteria. We aim to pilot a model of universal access to self-collection at primary care sites in rural and metropolitan Victoria providing evidence based recommendations to inform policy and practice on the expansion of self-collection.
Project: The SITA Trial (Should I Take Aspirin?): an RCT of a decision aid to support informed choices about taking aspirin to prevent cancer and other chronic disease.
Investigators: Prof Jon Emery (Lead Applicant), Prof Finlay Macrae, Prof Mark Jenkins, Dr Jennifer McIntosh, Dr Patty Chondros, Prof Lyndal Trevena, Dr Fiona Walter, Ms Sibel Saya, Ms Shakira Milton, Ms Julie Marker, Dr George Fishman, Mr Max Shub, Ms Sarah McGill, Ms Kate Broun, and Dr Sara Whitburn
Collaborating Organisations: University of Melbourne, Royal Melbourne Hospital, University of Cambridge and University of Sydney
Funding: $300,000 over two years
Project Description: Cancer Council Australia recently published evidence-based guidelines which recommend that people aged 50-70 years consider taking aspirin to prevent bowel cancer. Aspirin can reduce the risk of dying from bowel cancer by 33% but it also has potential side-effects including stomach ulcers and strokes. Most doctors and consumers are unaware of these recommendations. The SITA trial will test a novel decision aid in general practice, that summarises the evidence about the benefits and risks of taking aspirin and look its effect on people’s informed choices and subsequent use of aspirin.
Project: A randomised controlled trial of patient narrative SMS messaging in general practice to increase participation in the National Bowel Cancer Screening Program in Victoria
Investigators: Dr Jennifer McIntosh (Lead Applicant), Prof Jon Emery, Prof Mark Jenkins, Dr Tina Campbell, Ms Edweana Wenkart, Ms Lynne Jenkins, Mr Ian Dixon, Ms Julie Toner, Mr Tony Cowie, and Ms Clare O'Reilly
Collaborating Organisations: University of Melbourne
Funding: $300,000 over two years
Project Description: The Australian Government sends a free bowel cancer test to every person from the age of 50, however only 41% of people complete the test. We know that people are more likely to do the test if it is endorsed by their GP. We also know that people are influenced by stories they can relate to. Our research will test the use of an SMS message sent by the patient’s GP that includes a video of someone describing their positive experience about bowel cancer screening to increase uptake of the bowel cancer test.
2019 Workforce Funding Recipients
Early Career Research Fellowships (Biomedical Stream)
A novel therapeutic strategy for ovarian carcinosarcoma – blocking the EMT that leads to its formation
Ovarian carcinosarcoma is one of the rarest and deadliest forms of ovarian cancer. Ovarian carcinosarcoma is particularly aggressive as it is made up of two tumour types – epithelial tumour cells (carcinoma) and mesenchymal tumour cells (sarcoma). I hypothesise that the epithelial tumour transitions into a mesenchymal tumour through a process called epithelial-to-mesenchymal transition (EMT). In this project I aim to prove this and show that because of this phenomenon, EMT blocking drugs are more effective than standard chemotherapies for ovarian carcinosarcoma, therefore improving the outlook for patients with this type of cancer.
Real-time in vivo transcriptome profiling using circulating tumour DNA to predict response and resistance to cancer therapies
Tumours can shed small amounts of DNA into the patient’s bloodstream. Thus, a simple blood test presents a window to study the cancer and provides a ‘liquid biopsy’ alternative to often painful or impractical tissue biopsies. Each patient’s circulating tumour DNA (ctDNA) has the potential to be used as a personalised biomarker in managing their cancer. This research project will utilise ctDNA to study how breast cancers evolve when they progress and become resistant to treatment. This knowledge is expected to inform new strategies to improve current therapies and help individualise treatment decisions for breast cancer patients.
Does aberrant alternative splicing of RNA promote triple negative breast cancer?
This work aims to form a foundation for developing new ways to treat aggressive breast cancer. The discovery of effective treatments for aggressive breast cancer is a major area of unmet clinical need. Work in our laboratory has identified unique genetic signatures (found in the initial stages of breast tumour formation) that lead to abnormal gene regulation, which effects how genes are physically processed and therefore function. Using laboratory-controlled studies of breast cancer, we aim to uncover the role of these genetic signatures during tumour formation, particularly any genes that we can use to develop, target or deliver cancer therapies.
Early Career Research Fellowship (Biomedical stream) incorporating the Victoria-USA Cancer Fellowship Exchange Program
Identifying metabolic biomarkers and novel therapies in melanoma
Australia has the highest incidence of melanoma globally. Although targeted and immunotherapies have dramatically improved outcomes, we still do not fully understand why some patients relapse after surgery or why some melanomas do not respond to therapies. Understanding the fuels that tumours use to derive energy (metabolism) could potentially answer these questions. This project uses novel techniques to directly assess metabolism in mice and patients with melanoma. For the first time, we will comprehensively characterise melanoma metabolism in living tumours and ultimately aim to use this knowledge to improve diagnosis, predict outcomes and develop novel therapies for patients with melanoma.
Early Career Research Fellowship (Non-Biomedical Stream)
Reducing the burden of breast cancer by Precision Prevention: Improving breast cancer risk prediction by integrating comprehensive information
This project aims to develop an improved breast cancer risk prediction model by combining known risk factors and genetic variants with new emerging predictors such as epigenetics and breast tissue age. The risk model could be used in familial cancer clinics and screening programs, to assess the future risk of developing breast cancer for millions of women. It will provide evidence-based support for personalised breast cancer prevention and screening.
Mid-Career Research Fellowship (Biomedical Stream)
Novel blood-based biomarkers to guide immunotherapy management in early stage melanoma
Melanoma is the cause of most skin cancer deaths in Australia. While immunotherapy has revolutionised the treatment of melanoma, many patients experience profound toxicities to treatment. There is a critical need to better select patients likely to benefit from immunotherapy and predict responses from treatment for melanoma patients. We aim to develop accessible, minimally-invasive blood-based approaches to effectively guide the management of immunotherapy in melanoma patients. Our results will lead to better treatment options and improved outcomes for melanoma patients.
A multiple modality approach for targeting chemotherapy- and PARPi-resistant ovarian cancer
More than 1000 Australian women die of therapy-resistant ovarian cancer (OvCa) every year. My research is testing new approaches that we have pioneered to selectively damage the DNA of cancer cells to target ovarian cancer. A cornerstone of our approach is CX-5461, a new anti-cancer drug that we have developed and shown to work in drug-resistant blood cancers. We believe CX-5461 will be effective and less toxic than chemotherapy. This project aims to design new drug combinations with CX-5461 to enhance the therapy, prevent cancer relapse and provide much needed effective treatments for ovarian cancer patients.
Improving outcomes for poor risk acute myeloid leukaemia (AML)
The anti-cancer agents called BH3-mimetics targeting BCL-2 have altered practice for several blood cancers in the clinic. However, not all patients will respond to BCL-2 targeted therapies. I will explore the role of a new BH3-mimetic compound targeting a BCL-2 related protein called MCL1. I will demonstrate the efficacy of combining BCL-2 and MCL1 inhibitors to treat poor risk acute myeloid leukaemia (AML) and present new data exploring novel mechanisms of resistance, which are likely to impact on clinical practice. These studies will guide and refine the design of future clinical trials of BH3-mimetics in the treatment of AML.
Delivering new therapeutic opportunities in colon cancer
Despite a range of treatments available for colon cancer patients, the options for treatment of advanced stages when cancer has spread to other parts of the body is limited. My projects are focussed on developing new preclinical drugs that fight cancer spread. One approach is to take drugs that are already in the clinic and repurpose them as treatment for cancer. I have discovered that a drug commonly used to treat bone loss, has potent effects in experimental models of colon cancer. We aim to determine the effectiveness of this drug in colon cancer patients.
Enhancing muscle health to improve outcomes in cancer patients
Muscle health is closely linked with patient outcomes in many cancers. The healthier the muscle, the better the prognosis. In comparison, diminished muscle health is associated with a reduced response to cancer treatment, such as chemotherapies, resulting in a greater incidence of recurrence and reduced survival. This proposal seeks to understand the short and long-term effects of cancer and anti-cancer therapies on muscle health and to establish novel therapeutic strategies to enhance muscle health during treatment and in remission. These outcomes have the potential to transform current cancer treatments, improve clinical remission rates and enhance the prognosis for cancer patients.
Developing new therapies to improve Small Cell Lung Cancer patient outcomes
Small Cell Lung Cancer (SCLC) patients initially respond to front line platinum-based therapy, but then rapidly relapse with a uniformly fatal disease. This program will take advantage of our unique pre-clinical genetically engineered mouse models coupled with drug and genetic screening to identify new therapies that can overcome platinum resistance and define new therapeutic options for each of the newly described subgroups of SCLC. Finally, we will determine the ability of immune modulation to block metastatic spread and improve patient responses to the new classes of immune based therapies.
Development and characterisation of next generation BET inhibitors
The last decade has seen widespread enthusiasm around the development of novel epigenetic therapies for the treatment of many diseases, including cancer. BET-bromodomain inhibitors are amongst the most exciting, with remarkable pre-clinical efficacy paving the way for clinical trials. Unfortunately, while some patients are displaying a partial or complete response, the overall response rate has been disappointingly low. This is likely due to an incomplete understanding of the biological and tumorigenic role of the individual bromodomains and/or BET family members. Unravelling their distinct functions using both cutting edge pharmacological and genetic tools will drive improvements of these exciting new therapies.
Targeting cell survival pathways for cancer treatment
Many cancers remain incurable and require urgent research. Cancer cells often escape self-destruction leading to their unwanted persistence. Drugs that restore this normal capacity to self-destruct are proven to be clinically effective and form the basis of this proposal. We will investigate their potential for the treatment of incurable cancers (biliary tract cancers, uveal melanoma, mesothelioma) and prevention of patient relapse. Our studies will be amongst the first to investigate a new, safer and more effective version of these drugs. A successful outcome will have genuine potential for clinical translation and give hope to patients with a currently dismal outlook.
Mid-Career Research Fellowship (Non-Biomedical stream)
Supportive Care in Upper Gastrointestinal Cancer: Identifying patterns of use and examining barriers and enablers to access and uptake of services
People with pancreatic (PC) and oesophagogastric cancers (OGC) often have a high symptom burden and very poor quality of life. Even though management of symptoms and relief of suffering is the main priority as the search continues for treatments to improve survival, the supportive care needs of these patients remain largely unmet. The reasons for these unmet needs remains unknown. This project aims to understand the role of supportive care services in addressing unmet needs for patients with these cancers.
Embedding exercise into routine cancer care: Developing tools and strategies to support exercise advice by the cancer care team and exercise participation by cancer patients
If the effects of exercise could be encapsulated in a pill, it would be viewed as a breakthrough in cancer care and prescribed to every cancer patient. Unfortunately, patients can’t ‘take’ an exercise pill, they have to actively ‘do’ exercise to reduce the number and severity of cancer-related side-effects. Despite the potent effects exercise medicine can have in cancer care, 90% of patients don’t engage in evidence-based exercise. This project will evaluate how to most effectively assist cancer patients access exercise and develop pragmatic tools/strategies to help:
- health professionals prescribe exercise medicine; and
- cancer patients take exercise medicine.
Exercise oncology services closer to home: Improving equity of access and survivor outcomes through the development of a multi-disciplinary digitally-delivered service.
Access to exercise services that meet the unique needs of cancer survivors is currently limited, especially in regional and remote areas. This project aims to extend the reach of an established service that focuses on improving functional capacity among Haematology survivors before undertaking a stem cell transplant. To achieve this, a digital model of support will be designed and implemented in collaboration with survivors and the existing service delivery team and refined over-time based on on-going evaluation. The outcome will be a digital service ready for integration into care, and momentum for expanding the service to survivors of other cancers.
Clinical Research Fellowship
Immunoglobulin replacement versus Prophylactic Antibiotics to prevent infections in patients with hypogammaglobulinaemia due to blood Cancers Trials program (IMPACT)
Patients with blood cancers such as myeloma and lymphoma develop immune deficiency from low immunoglobulin (antibody) levels placing them at substantial risk of infection, which may be life-threatening. Immunoglobulin (Ig) products made from donated plasma are routinely used to supplement antibody levels to prevent infections in this setting, but there is little evidence on optimal use of Ig or alternatives. I will undertake clinical trials to identify which patients are most likely to benefit from Ig replacement and whether alternatives, such as antibiotics, could also be effective, aiming to improve patient outcomes, reduce risks and save precious community resources.
Assessing tumour and host biomarkers to understand responses of central nervous system lymphoma to immunotherapy
Primary central nervous system lymphoma (PCNSL) is a disease with particularly poor clinical outcome despite advanced chemotherapy treatment combinations followed by intensification with radiotherapy or stem cell transplantation for younger patients. These strategies are associated with significant toxicity and questionable evidence of benefit. Immunotherapies such as checkpoint inhibitors have revolutionised outcomes for poor risk cancers including resistant Hodgkin lymphoma, and the same genetic changes that make Hodgkin lymphoma particularly sensitive are also present in PCNSL. This project will assess the effectiveness of including checkpoint inhibitors in primary therapy for PCNSL and include genetic and immune biomarkers that may predict response.