2015 Funding Recipients

Dr Sashendra Senthi
Victorian Cancer Agency Clinical Research Fellowship
Monash University
Improving programmed death 1 inhibitor response against metastatic melanoma with radiotherapy: optimising combination treatment and utilising genetic biomarkers
Metastatic melanoma generally confers poor survival. While immune activating drugs can extend survival beyond 10 years for some, they cause significant toxicity without benefit in others. Combining these drugs with radiotherapy can improve the proportion that benefit. I seek to optimise the synergism between immune activating drugs and radiotherapy and reveal the genetics underlying response. This will improve metastatic melanoma survivorship, limiting treatment to those with a chance of response and cost-effectiveness, allowing more rapid approval of immune activating drugs for other indications.

Dr Mark Shackleton
Victorian Cancer Agency Clinical Research Fellowship
Peter MacCallum Cancer Centre
Translating melanoma dicoveries from the laboratory to the clinic
Cancers usually arise from one cell. However, as tumors grow, the cells that comprise them often become different from one another. The ability of cancers to produce diverse cell types is called cancer heterogeneity and is a major driver of cancer recurrence and of resistance to cancer treatment. My research will focus on understanding the nature of heterogeneity in melanoma, and how the body’s immune system reacts against tumors as they change and spread. I will also test new combination treatments as well as undertake clinical studies to account for the challenges presented by cancer heterogeneity in patient management.

Dr Gabriela Brumatti
Victorian Cancer Agency Mid-Career Research Fellowship
The Walter and Eliza Hall Institute of Medical Research
Identifying new therapeutic strategies using the new clinical drug birinapant, to overcome drug resistance and treat blood cancers such as Leukaemias
Acute Myeloid Leukaemia (AML) is an aggressive cancer of blood cells, affecting people of all ages. Less than 50% of AML patients can be cured with the current treatments. Thus, new therapeutic strategies are needed. We have been at the forefront of understanding how a new anti-cancer drug, birinapant, kills cancer cells. This project will test whether birinapant, in combination with other clinical drugs, can be used to treat leukaemia. The aim of our research is to determine how these drug combinations can be effectively used to increase the chances of cure, with reduced side effects, and benefit patients.

Dr Andrew Deans
Victorian Cancer Agency Mid-Career Research Fellowship
St Vincent's Institute of Medical Research
Improved Use of Gene Panel Testing in Familial Breast Cancer Clinics
Since 1997, genetic testing of BRCA1/BRCA2 has been offered to selected women attending Familial Cancer Centres in Victoria. For the majority of women (~85%) these tests are uninformative (negative). Continued research has identified additional genetic risk factors for breast cancer that have not been translated into clinical practice due to lack of evidence and defined process. This proposal will build the evidence base required for an expanded set of tests – “gene panel testing” – to be delivered. In particular, expertise in functional assays will be used to identify cancer-predisposing variants for risk estimation and clinical evaluation.

Dr Kylie Gorringe
Victorian Cancer Agency Mid-Career Research Fellowship
Peter MacCallum Cancer Centre
Personalised risk evaluation of ductal carcinoma in situ 
When a woman is diagnosed with ductal carcinoma in situ (DCIS), she is told by her doctor that there is a chance it will return as cancer. But what chance? The risk provided is an average and may not be accurate for her specifically. Wouldn't it be better to have precise, personal risk to base treatment choice on? Strong candidate biomarkers will be tested using clinical-grade assays on 200-400 DCIS tissues with patient outcome data. The best markers will be developed into a model to give a robust risk value on which to base treatment decisions.

Dr Lev Kats
Victorian Cancer Agency Mid-Career Research Fellowship
Peter MacCallum Cancer Centre
Development of personalised therapy for leukaemia based on a specific genetic mutation
Novel therapies for acute myeloid leukaemia (AML) represent an area of urgent unmet clinical need. Mutations in enzymes known as IDH1 and -2 are amongst the most common in AML and offer a promising opportunity for development of a new generation of targeted drugs that specifically kill leukemic cells without affecting normal tissues. Herein we propose to use advanced genetic and pharmacological tools to comprehensively analyse the role of IDH dysfunction in leukaemia initiation, development and progression. We expect that our findings will guide ongoing and future clinical trials for novel therapies of AML.

Dr Enid Lam
Victorian Cancer Agency Mid-Career Research Fellowship
Peter MacCallum Cancer Centre
Evaluation of tumour heterogeneity in the initiation and maintenance of AML and following response to therapy
The advent of global sequencing technologies has highlighted that every cancer displays marked heterogeneity in DNA mutations and gene expression programs. This intra-tumour heterogeneity underpins the unpredictable natural history of all malignancies including acute myeloid leukaemia. It is also the primary driver for the variable response often observed to conventional and targeted chemotherapies. Deciphering this complexity at the single cell level holds the key to a more comprehensive understanding of the biology of cancer. Furthermore, understanding the adaptive responses to therapies holds the promise of improving therapeutic outcomes.

Dr Rodney Luwor
Victorian Cancer Agency Mid-Career Research Fellowship
The University of Melbourne
Overcoming Tumour Resistance to Epidermal Growth Factor Receptor Targeted Therapy
Treatment of cancer patients using growth factor receptor inhibitors is only moderately successful due to resistance mechanisms developed by the tumour, which allow key pro-cancerous signals to continue, unaffected by treatment. We recently discovered a novel role of the key signalling molecule in cancer, STAT3 in mediating resistance to cancer treatment targeting the epidermal growth factor receptor. Therefore, this research project will evaluate the blockade of STAT3 as a method to re-sensitize tumours to anti-EGFR based therapy. This work will provide evidence for the use of such novel combinational therapy in cancer patients clinically.

Dr Ian Majewski
Victorian Cancer Agency Mid-Career Research Fellowship
The Walter and Eliza Hall Institute of Medical Research
New approaches to improve the diagnosis and clinical management of childhood cancer
Cancer results from mutations that disrupt the mechanisms that regulate cell growth and survival. Advances in sequencing technology mean that it is possible to profile a cancer to identify the mutations that supporting its growth. This application is focused on using this knowledge to match patients with effective therapies. While initially focused on childhood leukaemia, we aim to build new diagnostic systems that will improve outcomes for all cancer sufferers.

Dr Carl Walkley
Victorian Cancer Agency Mid-Career Research Fellowship
St Vincent's Institute of Medical Research
Development and application of preclinical models to improve cancer outcomes
I am interested in developing models of human cancer to improve our understanding of these cancers (bone cancer and blood cancer) and to use these models to identify and test new therapies.

Dr Renea Taylor
EJ Whitten Mid-Career Research Fellowship
Monash University
Targeting Castrate-Tolerant Prostate Cancer Cells
This proposal addresses one of the more important challenges in cancer: what cell population ‘drives’ cancer progression and how can it be effectively targeted? The goal is to define the prostate cancer cells that survive treatment and determine better ways to kill them. Eliminating these cells earlier in disease progression will lead to increased survival for men with prostate cancer.

Dr Dane Cheasley
Victorian Cancer Agency Early Career Seed Grant
Peter MacCallum Cancer Centre
Improving early detection and management of women at risk of developing interval breast cancer
Breast cancers diagnosed after a negative mammogram but prior to the next scheduled screening are termed “interval cancers”, and comprise 25-30% of breast cancers diagnosed in women undergoing population-based mammography screening. Interval cancers have a worse prognosis compared to screen detected cancer and is a key limitation on the effectiveness of population based mammographic screening. We will identify inherited features of interval cancers that can be used to prospectively identify women at risk of developing an interval cancer, so that modification of screening can reduce the interval cancer rate and reveal new treatment options.

Dr Elizabeth Christie
Victorian Cancer Agency Early Career Seed Grant
Peter MacCallum Cancer Centre
Clinical translation of a newly discovered transcriptional fusion involving the multidrug resistance transporter (ABCB1) in recurrent drug resistant ovarian cancer
We recently conducted the first whole genome sequence analysis of recurrent and end-stage high-grade serous ovarian cancer (HGSC) (Patch et al Nature 2015) and discovered fusion of the multidrug resistance transporter gene, ABCB1, to an upstream gene, resulting in profound overexpression of this drug efflux pump. Using unique patient derived cell lines with the fusion we will explore approaches to reverse drug resistance in recurrent ovarian cancer.

Dr William Figgett
Victorian Cancer Agency Early Career Seed Grant
The University of Melbourne
Development of monoclonal antibodies and chimeric antigen receptor T cells targeting the BAFF receptor TACI for treating chronic lymphocytic leukaemia in pre-clinical models
Chronic lymphocytic leukemia (CLL) is a cancer of the immune system cells, where cancer cells proliferate in the blood. The immune system is compromised, and recurrent infections are a major problem. We will generate antibodies that bind specifically to TACI, which is a receptor on the surface of some cancer cells and some types of immune system cells. We predict this will change the signals that are given by the cancer cells to repress the immune system, which would be reprogrammed to activate and help fight against infections and cancer. Alternatively we will modify immune cells to eliminate TACI-expressing cells.

Dr Jacqui Frowen
Victorian Cancer Agency Early Career Seed Grant
Peter MacCallum Cancer Centre
A prospective study of swallowing and voice outcomes after treatment for small-cell lung cancer
Lung cancer remains the most common cancer in the world, with high incidence and mortality rates. Patients with lung cancer are at risk of swallowing problems (dysphagia) and voice problems (dysphonia) due to the cancer itself or its subsequent treatment. Dysphagia in particular can be devastating, and if severe may cause fatal complications. This study will investigate swallowing and voice problems prior to and again after treatment in patients with small-cell lung cancer, to gain a detailed insight into the extent and nature of this problem so that patients can be more appropriately managed and significant treatment complications avoided.

Dr Lahiru Gangoda
Victorian Cancer Agency Early Career Seed Grant
La Trobe University
Understanding the molecular mechanisms regulating chemotherapeutic drug resistance
Bowel cancer is the most common form of cancer in Australia with 15,000 people diagnosed each year.  Chemotherapy is the first line of treatment to kill cancer cells in patients with advanced bowel cancer. Cancer patients may develop resistance to anti-cancer drugs resulting in the failure of the treatment. This project seeks to identify mechanisms by how cancer cells resist treatment. Furthermore, we will silence key proteins (identified in our preliminary analysis) that are thought to play important roles in developing drug resistance. Silencing these key proteins may result in efficient killing of cancer cells.

Dr Dale Garsed
Victorian Cancer Agency Early Career Seed Grant
Peter MacCallum Cancer Centre
A unique cohort of long-term survivors of high-grade serous ovarian cancer: Molecular insights into exceptional responses to chemotherapy
High-grade serous ovarian cancer (HGSC) is one of the deadliest cancers affecting women due the tendency of these tumours to develop chemotherapy resistance. This project aims to molecularly investigate why a small subset of patients with HGSC have an outstanding response to chemotherapy. Tumours collected from exceptional responders will be genetically profiled to identify changes in DNA associated with enhanced sensitivity to chemotherapy and long-term survival. We believe that understanding how these unusual women beat the odds may provide insights into improving outcomes of patients with HGSC that have a more typical disease trajectory.

Dr Lesley Stafford
Victorian Cancer Agency Early Career Seed Grant
Royal Women's Hospital
Development and evaluation of a brief psychoeducational intervention to support parents with cancer who have young children
Cancer in a parent with young children is stressful for the entire family. Parents have high rates of anxiety and depression and their children are at increased risk of poor psychosocial outcomes. Parents worry about meeting their children’s emotional and information needs and about the impact of the illness on their children. This project will develop and evaluate a novel, accessible and sustainable intervention to improve parenting skills, confidence and quality; enhance children’s psychosocial adjustment, reduce parental stress and psychological morbidity and improve family communication among parents receiving curative treatment.