2020 Workforce Funding Recipients
Early Career Research Fellowships (Biomedical Stream)
Novel therapies targeting HER2 in lung cancer
HER2 is a protein commonly expressed on cancer cells. Genetic changes in the HER2 protein promote cancer development and growth. In lung cancer, patients with HER2 alterations typically have aggressive cancers that respond poorly to chemotherapy and are associated with a poor prognosis. There are no approved drugs to target HER2 in lung cancer. In this proposal we will define the therapeutic benefit of a novel HER2 targeting drugs alone and in combination with immunotherapy in lung cancer models with HER2 alterations with the ultimate aim of extending this work to clinical trials.
Harnessing colon γδ-Τ-intraepithelial lymphocytes to improve immunotherapy and risk prediction in colorectal cancer
We found that immune cells in the colon called ‘gamma-delta-T-intraepithelial lymphocytes (γδ-Τ-ΙΕLs) prevent colorectal cancer (CRC) progression. The community of bacteria living in our bowel contribute to CRC. We found that antibiotics treatment changes these communities and modifies γδ-Τ-ΙΕLs function. I will uncover how γδ-Τ-ΙΕLs protect against tumour progression by investigating how they respond to bacterial changes and kill tumour cells. I will identify gene changes in γδ-Τ-ΙΕLs to assist in the development of new drugs; test new treatment approaches aimed at boosting γδ-Τ-ΙΕLs-mediated tumour cell killing; and identify bacteria/γδ-Τ-IELs gene changes that will highlight the risk of developing CRC.
Exploiting therapeutic vulnerability of Hedgehog activated osteosarcoma
Osteosarcoma is a highly aggressive tumour of bone, primarily affecting children and adolescents with dismal outcomes. Our recent observations implicating inactivation of the tumour suppressor genes, TP53 and RB1, in oncogenic Hedgehog (Hh) signalling has led to a renewed hope in developing potential targeted therapies for osteosarcoma. Using preclinical osteosarcoma models and patient tissues, we propose to evaluate response to Hh inhibitors in tumours harbouring mutations in TP53 and RB1 and identify synergistic therapies. Validation of predictive biomarkers of response to Hh inhibitor therapy and identification of novel synergistic drug combinations will lead to urgently needed improvements in patient outcomes.
Immune-based therapies (immunotherapies) such as immune checkpoint blockade and CAR T cell therapy have revolutionised the treatment of several cancer types. Despite this success, there remains numerous cancer types that are refractory to these therapies and an unacceptably high number of suboptimal responses. One key factor limiting their efficacy is the inefficient movement of anti-tumour T cells into the tumour site. This research proposal details the use of highly advanced screening methodologies and genetic engineering tools to improve T cell trafficking into tumours, with the intent of the broadening the range of patients that receive clinical benefit from immunotherapies.
Targeting cellular mechanisms that regulate the efficiency of protein synthesis to improve outcomes for men with metastatic castrate resistant prostate cancer
Prostate cancer is well managed clinically in its early stages. Unfortunately, in a significant proportion of patients, the disease will recur and eventually develop into lethal form known as "castration resistant prostate cancer". Current targeted therapies in prostate cancer have been mostly focused on inhibiting how testosterone works in the body, with limited success. Using animal models in which we implant and grow patients’ tumour samples, we will test whether the inhibition of the mechanisms by which cancer cells control how efficient they produce proteins is a viable approach to treat men with this lethal disease.
Early Career Research Fellowships (Non-Biomedical Stream)
Informing responses to late diagnosis and rising incidence of young-onset colorectal cancer: Understanding pathways to diagnosis and treatment to improve outcomes.
The number of people aged under 50 diagnosed with colorectal cancer is increasing. Younger people present with more advanced stage disease than older people, possibly due to delayed diagnosis, which results in poorer survival. Using surveys, interviews and linked health data, this project aims to improve our understanding of the pathway to colorectal cancer diagnosis and treatment of younger compared to older people. This research will explore whether, when and why there are delays, and strategies to improve the speed, experience of diagnostic pathways, and outcomes for the growing number of young people affected by colorectal cancer in Victoria.
The equity impacts and cost-effectiveness of targeted programs to increase bowel, breast and cervical cancer screening in disadvantaged groups in Victoria.
Early detection of cancer through screening saves lives. In Victoria, particular ethnic and lower socioeconomic groups have less than average participation in breast, bowel and cervical screening. This project will evaluate new programs designed to increase screening in these priority populations. The results will determine whether the programs provide value for money and have the desired effect of improving the long-term health outcomes of the priority population groups. This will help to ensure that resources are directed to the most efficient and equitable programs, giving Victoria the best chance of improving cancer inequalities amongst disadvantaged groups.
TeleCaRe: Expanding delivery of Cancer Rehabilitation via telehealth
Exercise-based rehabilitation is an essential part of cancer treatment and recovery. However, just 1 in 200 people can access exercise-based cancer rehabilitation. Consequently, people struggle to return to pre-cancer function which negatively affects their quality of life.
COVID-19 forced clinicians to embrace digital technology to provide healthcare. This project will evaluate a cancer telerehabilitation program rapidly developed in response to COVID-19. If comparable to traditional cancer rehabilitation, findings will be used to develop a high-value telerehabilitation package that can be readily scaled-up to other health services to extend the reach of exercise rehabilitation to cancer survivors.
Mid-Career Research Fellowship (Biomedical Stream)
Increasing immunotherapy efficacy against gastric cancer
Most advanced stomach cancer patients will die from their disease within one year despite chemotherapies. Immunotherapy is a promising new treatment, which activates immune cells to fight the cancer, but is only effective for some gastric cancer patients.
I have identified a molecule termed IL33, which controls communication between cancer -and immune cells, as a key factor promoting gastric cancer growth.
My aim is to demonstrate the efficacy of combining anti-IL33 and immunotherapy, leading the way to improve gastric cancer therapy outcomes. Additionally, I will establish an IL33 test to help select the most effective immunotherapies for individual patients.
The development of precision vaccines for devastating paediatric brain tumours
Brain tumours are the leading cause of cancer-related morbidity in children, and Diffuse Intrinsic Pontine Glioma (DIPG) is the deadliest paediatric brain tumour. All efforts for DIPG treatment have been unsuccessful, and with a median survival rate of only 9 months after diagnosis, there is an urgent need for viable options for DIPG treatment. Cancer vaccination is an emerging approach for incurable cancers. I have developed new technologies and discovered new classes of vaccine targets. I will identify, validate and evaluate vaccine targets to develop a preclinical data package to include in future DIPG immunotherapy clinical studies.
Optimising combination therapies for breast cancer
Despite significant advances in breast cancer treatment, resistance to therapies and disease recurrence remain a major cause of breast cancer related mortality for women and men worldwide. The tumour suppressor PTEN keeps multiple growth promoting factors in check and its loss causes treatment resistance and cancer malignancy. We have identified novel factors regulated by PTEN and aim to test how their targeting will affect tumour response to treatments and breast cancer progression in novel pre-clinical models with PI3K and PTEN mutations. These studies have the potential to inform better clinical treatments for breast cancer associated with loss of PTEN.
Combating gastric cancer drug resistance
Gastric cancer is a leading cause of mortality with only a limited number of treatment options. Most Gastric cancers initially respond to chemotherapy but eventually become resistant to therapy. By profiling 17 gastric cancer tumours and their adjacent normal tissue, we identified a new type of transcripts that are uniquely expressed in gastric cancer and not normal cells. Here we will use a high throughput approach to identify which of these transcripts induce drug resistance. These findings will lead to the development of new approaches to combat gastric cancer drug resistance.
Improving Bone Marrow Transplantation Treatment of Leukaemias by Donor/Recipient ‘Mismatching’
Killer-cell receptors are central to immune surveillance, controlling both T cells and Natural Killer cells. Currently, exploiting Killer-cell receptors in the clinic is hampered by our lack of understanding of the extreme diversity of receptor and ligand pairings. I have recently provided a framework to decipher this receptor/ligand code and will apply this to bone marrow transplantation for the treatment of leukaemia. These studies will underpin the development of new strategies for donor/recipient matching and for the prophylaxis and treatment of cytomegalovirus reactivation in transplantation.
Enhancing the efficacy of chimeric antigen receptor T cells in solid tumours
This project will further enhance the therapeutic application of a gene-engineering based immune therapy involving a patients' own immune cells. To date this form of therapy has been effective in blood cancers but not solid tumours. My research will employ novel technological and scientific methods to make these gene-engineered immune cells more effective against solid tumours. These findings have the potential to provide treatment options for multiple solid tumour types including Breast, Lung and Ovarian cancers.
High throughput discovery of synergistic drug combinations for patients with low-grade serous ovarian cancer
Low-grade serous ovarian carcinomas represent about 5 per cent of all epithelial ovarian cancers diagnosed world-wide, and are largely unresponsive to standard ovarian cancer chemotherapy. Little is known about alternative treatment strategies for those diagnosed, and yet these are urgently needed. We will systematically investigate novel drug combinations with a study of the key genetic determinants of response to these combinations in a large panel of patient-derived tumour cells. This innovative project is the first of its kind, and will highlight new treatment opportunities, and create immediate clinical drug development opportunities to significantly improve patient outcomes in this understudied and poor-outcome group.
Systematic Identification of Novel Immunotherapy Targets
Immunotherapy has revolutionised the treatment of cancer in recent years, however the majority of patients fail to respond or ultimately relapse. This project aims to use cutting edge technologies to identify new targets for checkpoint blockade immunotherapy and CAR T cell therapy. The ultimate aim is to boost the number of cancer patients who can gain long lasting benefit from these class of modern cancer therapies.
Teaching an old drug new tricks: re-purposing Emricasan for cancer immunotherapy
Immunotherapy has revolutionised cancer treatment but is only effective in 10-20 per cent of patients. Thus, new immunotherapy options are urgently needed. We have uncovered an entirely new approach to cancer immunotherapy that targets T regulatory (Treg) cells: an immune cell type that is an indicator of poor prognosis. We show that Emricasan, an existing drug developed to treat liver disease, can kill Treg cells and boost immunity to tumours. This proposal will explore how Emricasan might be used in the clinic. This work could lead to better treatment options and improved outcomes for thousands of cancer patients.
Mid-Career Research Fellowship (Non-Biomedical Stream)
Economics of Cancer Care across the Continuum in Victoria (ECCC)
Value for money is an increasing imperative as health care costs and community expectations rise. Using three worked examples in under-researched areas - smoking cessation pre-surgery, primary care dermoscopy for early detection of skin cancers, and timing of support services - this work will establish the cost-effectiveness of alternative ways of improving cancer outcomes in Victoria. This research, the first of its kind in Victoria and nationally, will enable evidence-based decisions on service delivery for reducing the proportion of Victorians diagnosed with preventable cancers, improving cancer survival rates and enhancing end-of-life care experiences.
EMergE: An Ehealth Model of Care for Paediatric Patients and Families at the End-of-Treatment for Acute Lymphoblastic Leukaemia
“We stood there at the winning post, worn out but got no sustenance”
There is a gap in multidisciplinary care for paediatric cancer patients once they finish their treatment and before they are eligible for survivorship programs. The end-of-treatment is often a difficult transition for patients and families. There is a missed opportunity to provide information, guidance and referrals to primary-care, educational and psychosocial services if needed. We will develop, implement and evaluate an innovative ehealth model of care for Victorian patients who have finished childhood leukaemia. treatment. We will examine the scalability of this model for other diagnostic groups.
Testing a genetics-specific patient screening tool to personalise cancer genetic counselling and improve patient outcomes
Genetic testing to identify an inherited predisposition to cancer is dramatically increasing to optimise cancer treatment and to define personal and family members’ cancer risks. Genetic counselling is a critical process supporting patients having genetic testing but increasing demand poses a threat to the quality of this care. Patient screening tools, such as the Genetic Psychosocial Risk Instrument, can reliably and efficiently identify patient needs. This project will test the effectiveness of this tool in improving patient outcomes and assess whether it can be implemented in genetic counselling practice. The outcome will be an integrated screening tool ensuring care quality.
TELE-CONNECT: TELehealth Exercise for CONtinence after GyNaEcological Cancer Treatment
This study (called TELE-CONNECT) is a telehealth program to deliver pelvic floor muscle training to women with gynaecological cancer who suffer from urinary incontinence.
Urinary incontinence affects around one-third of women causing significant physical, social, emotional and financial burden. The prevalence of incontinence is doubled in women with gynaecological cancer.
Although evidence supports pelvic ﬂoor muscle training as first-line treatment for urinary incontinence, it is not known whether this treatment is as effective for women following gynaecological cancer treatment. This will be the first randomised trial to address this vital clinical question using the novel method of telehealth.