2021 Workforce Funding Recipients
Early Career Research Fellowships (Biomedical Stream)
Developing new EphA3 targeted treatments for colorectal cancer
EphA3 is a protein which is expressed in most colorectal cancers. It is expressed in the tumour microenvironment (the structures, cells and molecules that surround and support tumours) where it plays an important role in promoting cancer growth. We are developing new drugs, anti-EphA3-ADCs, which target EphA3 in a very specific manner and deliver chemotherapy directly to EphA3-expressing cells to reduce cancer growth. Using laboratory colorectal cancer models, I will test the effectiveness of anti-EphA3-ADCs alone and in combination with existing treatments we use for colorectal cancer, with the ultimate aim of extending this work to clinical trials.
Development Of Advanced Molecular Imaging Biomarkers In Lymphoma Patients Treated With Novel Therapies
Lymphoma is a common cancer of the immune system. Despite effective regimens available, 30% of patients with aggressive lymphoma are resistant to standard treatments and die. Newer treatments called immunotherapy are used to attack the immune system.
Positron Emission Tomography (PET scan) using different types of injected radioactivity allows molecular imaging of the determinants of aggressive disease and outcomes using these novel treatments. I aim to optimise the analysis and use of PET to determine what PET biomarkers contribute to the prognosis, and image changes in the immune system which occur with novel treatments to improve prognosis and disease understanding.
Therapeutically targeting cortactin: a novel mediator of cancer-induced cachexia
Cancer cachexia is a wasting disease that leads to the break-down of skeletal muscle and fat tissue. This disease effects 65% of all cancer patients and accounts for 35% of cancer-related deaths. Additionally, cancer cachexia reduces mobility, quality of life and anti-cancer treatment efficacy. Previously, we have shown that genetic deletion of cortactin (cell-structural protein) inhibits cancer cachexia whilst reducing tumour size and dramatically extending the lifespan of the tumour-bearing mice. With this, we have repurposed a previously FDA approved drug known as Dastinib, which reduces cortactin levels in cell culture. This reveals a novel approach for treating cancer cachexia.
Defining the Immunophenotype of durvalumab resistance with durvalumab and T-cell PET/CT
We will use 2 new PET tracers that show us if cancer cells take up durvalumab, an immunotherapy that improves survival in lung cancer, and tells us where the cancer killing T-cells are located.
In the first study we explore the biology of palliative radiotherapy. If it makes immunotherapy work better this will make it more effective for a wider group of patients.
In the second study we will explore the biology of the immunotherapy resistant patients, to see if the therapy resistance is because their cancer stops taking up durvalumab or it is because the T-cells are not effective.
Boosting the efficacy of BH3-mimetic drugs for hard-to-treat lymphomas
Patients with aggressive blood cancers face limited treatment options and poor prognosis. BH3-mimetic drugs represent promising new treatments for blood cancers. However, while most patients initially respond well to treatment, the majority eventually develop resistance and relapse. This project aims to design and test new evidence-based combination therapies to boost the effectiveness of BH3-mimetic drugs for patients with aggressive blood cancers. By evaluating new treatments in laboratory models and patient tumour samples, we will generate pre-clinical evidence to justify new clinical trials for blood cancers and improve patient outcomes.
Improving the prediction of metastatic spread in breast cancer patients leveraging immune cell communication profiles
Breast cancer kills eight women in Australia every day. Twenty percent of patients develop metastases. A proportion of these patients can control the metastatic spread and have a good life expectancy.
I have identified dramatic changes in the patterns of immune cell communication between the long-term metastatic survivors and the ones entering fast progression.
I aim to build a diagnostic tool to track the ability of a patient to control metastatic spread based on immune cell communication markers. This will enable better-targeted treatments and avoid overtreatment. Patients will be relieved from the stress of an uncertain rate of metastatic progression.
Identifying rational approaches to enhance the activity of the anti-cancer drug venetoclax
Venetoclax has proven to be highly effective for treating patients with chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML), prompting the regulatory approvals for the use of venetoclax to treat these patients. Unfortunately, the leukaemia will eventually recur in most patients, and further treatment options are then limited. The focus of my research is to discover novel approaches to enhance the efficacy of venetoclax. I plan to investigate the effect of venetoclax on the immune system and determine if venetoclax is compatible with newly emerging cancer immunotherapies. Ultimately, this study will lead to significantly improving patient outcomes.
Early Career Research Fellowships (Non-Biomedical Stream)
Lung Cancer Rehabilitation: standardising evaluation and co-designing a program for people during immunotherapy. The UNITE study.
People with lung cancer experience debilitating symptoms and functional loss. Rehabilitation is effective in improving function and quality of life and reducing symptom severity. There is little agreement regarding measurement of rehabilitation effects and limited knowledge regarding feasibility during immunotherapy. This project aims to improve survivorship for people with lung cancer by 1) standardising measures and 2) co-designing, with patients/carers, and testing rehabilitation during immunotherapy. A standard set of patient-centred measures (questionnaires, walking tests) for clinicians to assess rehabilitation effectiveness and improve program quality will be developed. The feasibility and patient acceptability of rehabilitation during immunotherapy will be determined.
Mid-Career Research Fellowships (Biomedical Stream)
New labelling strategies to study tumour cells and surrounding normal cells and identify new treatment options for aggressive breast cancer
Breast cancer is the most commonly diagnosed cancer in Australia and worldwide. In 2020, there were 2.3 million new cases and 685,000 deaths. The mortality associated with breast cancer is due to the ability of a few cancer cells, present in the primary tumour, to leave the breast, lodge in vital organs and escape from immune control and standard therapy. The objective of this proposal is to use new labelling strategies to study cancer cells and surrounding normal cells (including immune cells) and to propose new therapies to improve the outcomes of patients with breast cancer.
Targeting mammary adipose tissue-resident Tregs to improve immune checkpoint blockade therapies against breast cancer
In Australia, one in 8 women and one in 1,000 men develop breast cancer, and each year, more than 3000 patients lose their lives due to this disease. Immunotherapy has emerged as a game-changer for treating several cancers but has had more limited success in treating breast cancer. My overarching research goal is to improve outcomes for breast cancer patients by targeting a unique component of the immune system that suppresses anti-cancer immunity in breast cancer, which we identified as regulatory T cells expressing ICOS and ST2 genes. I will explore the therapeutic potential of targeting these immune suppressive cells.
Towards new therapeutics for neurofibromatosis-linked cancers and tumour growth
Mutation of the neurofibromin (NF1) gene cause the common genetic disease neurofibromatosis type 1 and drives many cancers, including neuroblastoma, melanoma, and brain cancer. This year my team made a breakthrough and solved the protein structure of NF1. This information provides the first complete and detailed map of the shape of the gigantic NF1 protein. I will apply new technologies to determine how these diseases alter the NF1 protein's function at the atomic level and inside the cell. This project will discover new pathways for therapeutic intervention for Australians living with NF1-linked cancers and tumours.
Leveraging cancer susceptibility genomics for improved precision public health and personalised clinical management
Genetic tests are an efficient way of predicting, mitigating and preventing disease as they can identify those who harbour genetic changes that put them at high risk of developing cancer.
Access to these tests is restricted and, consequently, their potential to be useful for detecting those at high risk is greatly reduced. We are also limited in our ability to interpret the clinical importance of some test results.
This project aims to i) create a cost-effective test that could be offered to all Australians by the healthcare system and ii) advance our understanding of the genetic test results.
Developing new therapies and early detection strategies for inherited cancer predisposition
My research will lead to the development of new cancer treatments for clinical trials that will benefit people affected by familial low-survival cancers. These drugs will target the Achilles' heel of a cancer cell and leave healthy cells unharmed. Because of the way they are designed, these drugs could be used at lower doses and would have less side effects than traditional chemotherapy. An additional study arm will enable new diagnosis and preventative cancer-screening methods for familial cancer predisposition syndromes.
Investigating Treatment Response in Women’s Cancers
My vision is to generate new knowledge of the treatment resistance mechanisms that arise in women with ovarian and endometrial cancer, and identify effective treatments to overcome resistance. Part 1 of my program involves examining the evolution of tumours to discover resistance mechanisms, and Part 2 involves translational studies to identify treatments and biomarkers.
This study is designed to address current gaps in knowledge so that findings can be rapidly translated into the clinic, transforming the clinical management of women’s cancers and improve survival outcomes.
Adjuvant immunotherapy to improve the efficacy, durability, and cost effectiveness of CAR T-cell therapy for aggressive lymphoma
Chimeric Antigen Receptor (CAR) T-cell therapy is an exciting new treatment for patients with blood cancers that uses a patient’s own immune cells to attack and destroy cancer. Some patients are cured who previously would have had no good treatment options, however these are in the minority. This clinical trial will test a range of possible additional drugs that are given before, during or after CAR-T cell therapy with the aim of increasing the long-term cure rate of CAR-T therapy. Patient samples will be used to better understand the immune response that results in cure.
Too tired to function: overcoming immune exhaustion to treat solid cancers
CAR T cell therapy is where a patients’ own immune cells are genetically engineered to attack and kill cancer cells. While this therapy works well against blood cancers, it is less effective against solid tumours because of a process called “exhaustion” that suppresses the CAR T cell response against the cancer. My research proposal will use cutting-edge genetic engineering to manufacture “exhaustion-resistant” CAR T cells to better treat a range of solid tumours, such as breast, lung, ovarian and colon cancer.
Mid-Career Research Fellowships (Non- Biomedical Stream)
Clinical Decision Support Systems for Cancer Prevention and Early Cancer Detection in Primary Care
These set of studies aim to address the problem of delays in cancer diagnosis in primary care. Clinical Decision Support Systems (CDSS) are tools to help clinicians identify at risk patients and provide the best available evidence for adequate follow up. We will develop and implement cancer risk models to identify patients who may be at risk of undiagnosed cancer to prompt further investigations through a CDSS for early cancer diagnosis in Victorian general practices.
EASI-M: A mobile health intervention to increase participation in cervical screening through self-collection
Cervical screening can prevent the development of cervical cancer. However, many people with a cervix do not participate in Australia’s cervical screening program. Recently, a new screening option, called self-collection, has been introduced. Self-collection allows participants to collect their own sample, mitigating many barriers to screening. This successfully encourages more people to screen. However, in Australia, awareness is low, and uptake has been very limited. I aim to develop and test a simple, acceptable and feasible SMS tool for primary care practices to use to raise awareness of self-collection and provide tailored support to encourage participation of for under-screened people.
Quality and Safety in Cancer Care Research Grant
HER2 testing in advanced gastric cancer – understanding and reducing variation in current practice to improve patient survival
Recent research has shown that HER2 plays a significant role in advanced gastric cancer and, that if patients are HER2-positive, treatment with targeted drug therapy substantially improves patient outcomes. Therefore, it is recommended that all patients with advanced gastric cancer are tested for HER2 status at the time of diagnosis. Due to the diverse expression of HER2, which can lead to false-negative test results, standard testing algorithms have been developed. However, our preliminary data suggests that not all patients with advanced gastric cancer are being adequately tested, with these patients not having the opportunity to benefit from targeted drug therapy.
BETTER-TRACC - BEnchmarking and Tracking TrEatment and ResulTs in the Routine care of Advanced Colorectal Cancer
As more treatment options become available for patients with metastatic colorectal cancer it is essential that these are used appropriately, safely and consistently to ensure optimal patient outcomes. Preliminary data from a cancer registry analysis indicates marked and concerning variation across Victorian hospitals in patient care and in survival. Through a consumer-clinician partnership, BETTER-TRACC will explore this existing registry data to better understand treatment and outcome variation across sites. We will then develop novel quality indicators and pilot quality appraisal reports for each hospital which outline performance compared to de-identified peers, identifying for each site opportunities for improved patient care.