2023 Workforce Funding Recipients
Low-Survival Cancer Philanthropic Research Fellowships
EMBRACE – Enhancing Multi-site BRAin Cancer research to advance discovEry
Glioblastoma is the most aggressive brain cancer with 5-year survival less than 5%. Treatment options remain limited, with inadequate bench-to-bedside translation. This project aims to leverage the infrastructure created by myself, and supported by existing collaborations, to improve translation of scientific discovery into survival benefit for patients. Using innovative models to replicate tumours within the individual, we aim to understand why glioblastoma remains resistant to traditional therapies and identify new targets and drugs for treatment. The outcomes will be a collaborative research ecosystem with enhanced research efficiency, more clinical trial activity, additional therapies for patients and ultimately improved survival.
Delving deep: uncovering genomic mechanisms driving rare low surviving ovarian cancers
Low Grade Serous Ovarian Carcinoma (LGSOC) is a rare form of ovarian cancer associated with poor survival. For the past 30 years, current treatment strategies have been based on that used for more common types of ovarian cancer, however these drugs fail in 70% of LGSOC patients. Using the world’s largest cohort of LGSOC patient samples our study will look at what DNA changes (mutations, methylation) cause LGSOC. We will then test FDA approved drugs that can target these changes to offer new treatment avenues. This study is designed so that results can rapidly transform LGSOC clinical management and improve survival of women diagnosed ovarian cancer.
Early Career Research Fellowships (Biomedical)
Identifying novel biomarkers for immunotherapy response in breast cancer
Few effective targeted therapies exist for triple negative breast cancer (TNBC), a subtype that accounts for 10-15% of breast cancers in Australian women. Immunotherapy has recently been approved for TNBC, however response rates are lower than in other cancer types. Using novel sequencing and imaging techniques, this project will map out the molecular identity and location of every cell in tumour samples taken from breast cancer patients before their treatment with immunotherapy. We will use this information to develop better criteria to identify patients who are unlikely to respond to immunotherapy, as well as combination treatments to overcome this resistance.
Enhancing Chimeric Antigen Receptor T cell efficacy against solid tumours
Chimeric Antigen Receptor (CAR) T cells is a treatment approach which involves the education of patients’ own T cells to recognise and attack tumours. This approach is highly successful (>90% response rate) in treating blood cancers but not against solid tumours (<5%). Evidence in our lab suggests that targeting the lymph node adjacent to the tumour could be the key to enhancing CAR T cell activation and function. This project aims to identify key regulators associated with CAR T cell activation in the lymph nodes and approaches to target lymph nodes to improve CAR T cell efficacy against solid tumours.
Early Career Research Fellowships (Non-biomedical)
Implementation of risk-stratified population screening for Australia’s most common cancers
A DNA risk test (called a polygenic risk score) can predict an individual’s risk of cancer and recommend the best type of cancer screening for their risk. Implementing this test for all Australians in a risk-stratified cancer screening program could result in more cancers detected early. This proposal will establish how such a program could be implemented for melanoma, breast, bowel, and prostate cancers, by consulting key stakeholders in policy, cancer screening, and the community. Additionally, it will determine how best to offer a DNA risk test in general practice, as the first point of healthcare for most Australians.
Mid-Career Research Fellowships (Biomedical)
A novel pan-cancer liquid biopsy for the early diagnosis of cancer
Cancer cells are detected by the immune system via unique molecules, tumour antigens. Immune cells can recognize these as foreign and produce antibodies that are released into the blood against them. I will investigate the clinical translatability of an innovative, sensitive blood-based tool capable of detecting these antibodies. I will screen large cohorts of high-incidence and low-survival cancers to determine antibody profiles unique to each cancer type. These profiles can be used to detect cancer onset early, preventing undetected disease progression and leading to improved patient outcomes.
Developing a blood test to enhance care for high-risk myeloma
Multiple myeloma (MM) is a bone marrow cancer with over 2400 cases in Australia annually and a 5-year survival rate. We currently face two significant challenges: firstly, there is difficulty in identifying individuals at risk of developing MM from early stages, and secondly, predicting relapse in MM patients post-treatment remains elusive. While genomic exploration offers a solution for identifying these high-risk patients, traditional genetic studies using bone marrow biopsies face limitations in invasiveness, access, and reliability. I propose overcoming these challenges by analysing small DNA fragments released into the blood by MM cells, aiming to define the genome of high-risk individuals. This approach seeks to pave the way for a non-invasive, patient-friendly blood test to provide personalised treatment strategies tailored to the unique genomic profiles of MM patients.
Exploring the role that metabolism and plasticity play in NRF2-driven liver cancer
Liver cancer is one of the deadliest cancers. Liver cancer arises from a combination of genetic mutations that conspire with environmental risk factors. Together these genetic and environmental factors reprogram the metabolism of cancer cells to drive tumour progression. The NRF2 pathway is frequently activated by mutation or environmental factors in liver cancer. Despite this understanding, the role that metabolism plays in NRF2-driven liver cancer is poorly understood. In this project, we seek to discover how NRF2-induced changes in metabolism initiate tumorigenesis. With this knowledge, we hope to identify metabolic vulnerabilities that can be targeted as therapies against liver cancer.
A sensitive test to detect the spread of stomach and oesophageal cancers in the peritoneal cavity: A prospective multicentre clinical trial
An accurate test to detect the early spread of stomach and oesophageal cancer in the abdominal cavity (peritoneum) is urgently needed. Peritoneal tumour DNA (ptDNA) is cancer-derived DNA detectable in peritoneal washings. In this study, we will recruit 200 patients with stomach and oesophageal cancer, and test their peritoneal washings collected as part of routine investigation, for ptDNA. We will compare two novel methods to detect ptDNA, and correlate ptDNA status with patient outcomes. This study will produce an accurate molecular test to detect microscopic peritoneal cancer deposits. This information will facilitate patient counselling, inform decision-making, and personalise cancer care.
Using novel pre-clinical models to prioritise the most effective targeted therapy combinations for high-grade serous endometrial cancer clinical trials
High-grade Serous Endometrial Cancer (HGSEC) is an extremely aggressive rare cancer that responds poorly to standard chemotherapies, leading to early death in ~80% of cases. HGSEC has a number of features that may make them sensitive to targeted therapies that are being used successfully to treat other cancers. However, these therapies have not been fully tested nor approved for this rare cancer and early studies indicate HGSEC is more complex and treatment resistance is a big problem. Using novel models of HGSEC we will study cancer development and the best combination therapies to prevent drug resistance and improve patient outcomes.
Advancing the clinical use of MCL-1-targeting BH3 mimetic drugs for cancer therapy
MCL-1 is amongst the most highly expressed oncogenes in human cancer and there is no doubt that targeting MCL-1 can kill cancer cells. Excitingly, MCL-1 inhibitors were shown to be highly effective in early clinical trials but some severe on-target side effects to healthy tissues were observed. MCL-1 ensures cell survival by blocking a programmed form of cell death. In addition, MCL-1 regulates cellular energy production. This project aims to better understand MCL-1’s protein functions in cancer as well as healthy cells and thereby allow a more efficient cancer cell killing while sparing healthy tissues.
Mid-Career Research Fellowships (Non-biomedical)
Enhancing Care for Blood Cancer Patients in Australia: Unpacking Workforce Requirement, Burden of Disease, and Care Pathway
Blood cancer is a major cause of cancer-related deaths in Australia, with projected lifetime costs of $10.9 billion for new cases by 2035. The National Strategic Action Plan for Blood Cancer 2020, endorsed by the Australian Government, envisions transformative approaches to treatment and care nationwide. The overarching aim of this fellowship is to provide crucial evidence to inform the implementation of the National Strategic Plan and assist with policy decision-making and resource allocation for blood cancer.
The outcomes from this fellowship will include readily interpretable evidence to guide the implementation of the National Strategic Plan in Victoria and nationwide, enhancing outcomes for people affected by blood cancer. I have consulted with haematologists and consumer representatives in developing the proposed research program and will engage policymakers through the investigator team to facilitate research translation.
Improving cancer care across rural Victoria: understanding and impacting on barriers to optimal care
People from rural areas experience poorer cancer outcomes than people from metropolitan areas and addressing this gap is a priority. There are few studies that have focused on understanding the reality and challenges of rural cancer care. We will conduct a large statewide survey to identify the factors of delays to cancer diagnosis. These factors will be explored by interviewing people with cancer and stakeholders and solutions will be generated. Finally, we will perform modelling to identify which solutions represent best value for money. This work has potential impact to improve rural cancer care across the state and country.
Palliative Care Cancer Research Grants
Implementation of timely referral to outpatient palliative care services in regional Victoria: is it possible to improve outcomes? (TROPICAL-VIC)
There is a growing body of evidence that for people with advanced cancers, early referral to palliative care services brings many benefits to patients, carers, and the health system. This study, co-designed with consumers, will develop and evaluate a model of early referral to a palliative care clinic. This model will include routinely asking all people with advanced cancer about their needs. Palliative care services in our region are underdeveloped and this will help improve the capacity and efficiency of services, help prioritise and address the needs of patients with advanced cancer and their carers, and improve inequity of access.
Evaluating Partially Ablative Body Radiotherapy (PABR) as a novel palliative approach for large inoperable and incurable, localised or metastatic sarcomas.
Patients who have bulky, inoperable tumours often experience symptoms resulting from the pressure exerted by these tumours. This leads to decreased quality of life and poses challenges for caregivers and healthcare providers. Our study uses a novel technique for delivering palliative radiotherapy, which delivers significantly higher radiation doses to the central region of the tumour while maintaining a lower dose to the surrounding areas. In comparison to conventional palliative radiotherapy, this approach has the potential to provide superior symptom relief, tumour shrinkage, longer response duration and improve quality of life without increasing toxicity, even in patients with poor performance status.
The implementation of early palliative care for people with high grade glioma: understanding effectiveness, costs and the role of telehealth
While there is strong evidence showing the benefits of early palliative care for patients, families and health systems, access to these services varies significantly, depending on diagnosis, geography and often, on luck.
We have developed a model of early palliative care proven to address existing barriers, which standardises delivery and ensures access to all. We will implement this model for people with brain cancer using face-to-face and telehealth models to ensure access for all Victorians. We will test the effectiveness and detail the costs and cost savings. Understanding these factors will inform the broader roll-out and sustainability of this innovative model of care.