“CCQ is the only reason I am able to continue my research into improving survival rates in head and neck cancer and breast cancer”. Dr. Fiona Simpson – CCQ research grant recipient.
In 2016 Cancer Council Queensland committed nearly $7 million towards its external funding program. This funding goes towards supporting cancer research throughout the state in the form of project grants, fellowships, travel/study grants and scholarships.
You can read about our recently awarded cancer research project grants below.
Current Cancer Research Project Grants
2018 – 2019
Prof Riccardo Dolcetti, The University of Queensland
Improved antigen-specific immunotherapy for cutaneous malignant melanoma
Novel drugs able to stimulate immune system to attack cancer have shown promising results in advanced melanoma, the most deadly skin tumour. Currently, however, these drugs are only effective in a subset of cases. The proposed studies seek to develop methods to enhance the efficacy of immune-based therapies by testing a novel strategy able to allow each melanoma patient to mount effective immune responses against his/her own tumour.
Prof Gregory Monteith, The University of Queensland
Pharmacological targeting of an adaptive breast cancer cell survival pathway as a novel treatment for breast cancer: Constitutive Ca2+ influx mechanisms in triple negative breast cancer cells
Women with triple negative breast cancer suffer from a disease for which new targeted therapies are required. This grant builds on data suggesting that adaptive changes in the activity and/or levels of specific proteins involved in the entry of calcium are a feature of some triple negative breast cancers. Inhibiting the activity of these proteins represents a novel way to induce and/or promote the death of these breast cancer cells and this grant explores this possibility.
Dr David Fielding, The University of Queensland
Streamlining lung cancer diagnosis through genomic testing of cytology smears
Chest physicians and pathologists at the Royal Brisbane and Women’s Hospital will spearhead research to give lung cancer patients the latest genetic tests to provide a clearer picture of their disease and how best to treat it. Patients and doctors from six Australian hospitals are involved. The study adds genomic sequencing to the current procedures for diagnosing lung cancer from lymph node samples, providing patient specific tumour mutation information which doctors can use to guide therapy.
Prof Paul Alewood, The University of Queensland
Development of oxytocin receptor specific tracers for improved breast cancer management
Breast cancer is still the number one cancer killer for women globally and current tumour detection procedures are suboptimal. This project investigates the oxytocin receptor as a promising new target for tumour diagnosis and therapy. Our combination strategy including advanced tumour visualisation and targeted radiotherapy is expected to substantially improve survival rates.
Prof Brian Gabrielli, The University of Queensland
Preclinical development of combinations with CHK1 inhibitors in melanoma and lung cancer
By selectively targeting defects that are specific for a tumour, it is possible to maximise the anti-tumour effect and minimise the often serious side effects associated with chemotherapy. Here we test in pre-clinical models of melanoma and non small cell lung cancer the mechanism and efficacy of the combination of a new targeted drug with sub-clinical doses of an old, well tolerated chemotherapy.
Prof Jean-Pierre Levesque, The University of Queensland
Colony-stimulating factor 1 receptor tyrosine kinase, a new target to treat acute myeloid leukaemia
This project is to investigate how a specific inhibitor of a receptor present on acute myeloid leukemia (AML) cells increases the efficacy of chemotherapy. 75% of adult patients with AML are not cured with chemotherapy and die. We have found in our pre-clinical model that this inhibitor combined with chemotherapy eliminate residual leukaemia cells that resist chemotherapy and cured of the disease. This project could lead to better treatments for AML leading to higher survival of AML patients.
Dr Kate Gartlan, QIMR Berghofer Medical Research Institute
Characterising IL-5 mediated suppression of alloimmunity
For many blood cancer patients the only curative treatment is donor stem cell transplantation, however complications arise in most recipients (>50%) due to graft-versus-host disease (GVHD). We have identified a novel and highly protective signalling pathway in recipient tissue that attenuates acute GVHD early post-transplant. This study will explore the therapeutic potential of promoting this regulatory pathway to prevent GVHD.
Prof Mark Smyth, QIMR Berghofer Medical Research Institute
Inhibiting ILC1 formation in cancer
We have discovered that transformed growth factor-beta (TGF-β), a protein made in growing tumors, is able to change white blood cell natural killer (NK) cells into related type 1 innate lymphoid cells (ILC1s), which actually help rather than hinder cancer’s growth and spread. We now wish to study tumor ILC1 and create new antibody molecules that prevent ILC1 generation. This new class of immunotherapy will be tested in preclinical mouse models with the aim of translating into the clinic.
Associate Prof Kelli MacDonald, QIMR Berghofer Medical Research Institute
Analysis of pathogenic macrophage differentiation and function in chronic GVHD
Leukaemia and lymphoma are responsible for about 10% of all cancers in Australia, and about 11% of all cancer deaths. Stem cell transplantation is the most effective and common treatment for these blood cancers, however, the procedure comes with the risk of developing graft-versus-host disease which can be fatal. We have identified a role for a specific immune cell in the development of graft-versus-host disease and expect to be able to modify this population to improve transplant outcomes.
Dr Jill Larsen, QIMR Berghofer Medical Research Institute
Identifying ‘cooperative’ mutations in non-small cell lung carcinoma that facilitate lung carcinogenesis
Lung cancer is the most common cause of cancer-related death in Australia. Targeted therapies specifically target a genetic alteration only in tumour cells and show extraordinary potential. This research will use a unique cell culture-based model that simulates lung cancer development to identify genetic alterations involved with changing normal lung cells into tumour cells. These alterations may identify new targets for drug design and advance our understanding of lung cancer development.
2017 – 2018
Prof Elisabeth Isenring, Bond University
Supplemental Prophylactic Intervention for Chemotherapy-induced Nausea and Emesis (SPICE) trial
Despite advances in anti-vomiting medication, nausea is still rated as one of the worst side-effect of cancer treatment and can result in strong reductions in quality of life. Previous studies suggest that ginger supplementation in conjunction with standard anti-vomiting medication, is effective in the treatment of chemotherapy-induced nausea. However, due to existing limitations within the literature, high-quality studies are needed to investigate this area further. The Supplemental Prophylactic Intervention for Chemotherapy induced nausea and Emesis (SPICE) trial will investigate whether ginger supplementation is more effective than a placebo in reducing the symptoms of nausea and improving quality of life for cancer patients receiving chemotherapy.
Dr Li Zhang, Menzies Health Institute QLD, Griffith University
Prevention of central venous catheter infection and occlusion by needleless connector design and disinfection in haematology-oncology patients
Australian cancer patients use 20,000 central venous catheters (CVCs) each year for anti-cancer therapy, transfusions, hydration, nutrition, and repeated blood tests. Around 1600 potentially fatal Central Line-Associated Bloodstream Infections (CLABSIs) occur annually and 13 per cent of CVCs become occluded causing CVC failure and replacement procedures. The annual cost of such complications exceeds $595 million, with pain, treatment delays, prolonged hospitalisation, and up to 25 per cent CLABSI-associated mortality. Better design and disinfection of connectors is vital to prevent CLABSI and CVC occlusion, improve patient outcomes and reduced costs, yet little clinical trial evidence is available.
The study is a multi-centre, 2×2 factorial, parallel randomised control trial to compare two connector designs (Positive vs Negative displacement design [controls]), and two disinfection (Chlorhexidine in Isopropyl alcohol vs. Isopropyl Alcohol [controls]). We will test the effectiveness of these treatments and hypothesise CLABSI will be reduced from 8 per cent to 4 per cent and occlusion from 13 per cent to 4 per cent. Adult cancer patients will be studied at two major hospitals in Brisbane. Embedded in the randomised control trial is a formative, qualitative evaluation to ensure rapid knowledge translation of results, and a microbiology study of the interaction between connector design, disinfection, colonisation, and infection.
Dr Lionel Hebbard, James Cook University
Clarifying the controversial role of fructose in liver cancer
Liver cancer or hepatocellular carcinoma (HCC) accounts for 1800 deaths/year in Australia and its incidence is expected to triple by 2030. Mortality from this disease is unacceptably high, with five-year survival below 16 per cent. It is estimated that at least a third of future liver cancer cases will be due to fatty liver disease, but how obesity and a fatty liver promote cancer growth is unknown. High carbohydrate intake and especially increased fructose consumption, is a major component of the western diet, and is believed to drive HCC formation. Fructose has distinct and divergent metabolism as compared to glucose and in our studies with liver cancer cells and genetic mouse models, we have found that fructose promotes the upregulation of specific metabolic pathways in vitro and in vivo. Moreover, being overweight or obese is associated with low levels of serum adiponectin, and this is in turn a driver of HCC growth. We have found that adiponectin modulates HCC growth in the presence of fructose. Thus, our principle objectives are to examine the role of fructose and adiponectin in: (i) metabolic signalling and HCC cell survival, and (ii) the genetic regulation of liver cancer growth. This will be achieved by using HCC cell lines and tumour models, with specific antagonism of tumour metabolism, and testing the function of genes that adiponectin regulates in HCC growth.
Dr Antiopi Varelias, QIMR Berghofer Medical Research Institute
Understanding the interplay between cytokines and intestinal dysbiosis following stem cell transplantation
Stem cell transplantation (SCT) is the only curative treatment option for the majority of haematological malignancies. However, the success of this treatment is limited due to major complications, principally graft-versus-host disease (GVHD) whereby cytokines and donor T cells cause extensive tissue damage. This occurs in the majority of transplant patients (50-70%) with acute GVHD of the gastrointestinal tract commonly being lethal. A better understanding of the disease process is required to make this procedure safer and improve transplant outcomes. The integrity of the gastrointestinal tract is highly sensitive to inflammatory cytokines, mediators of the immune response, while the role of gut bacteria is beginning to be better appreciated. Antibiotic-based approaches to deplete the gut bacteria and prevent acute GVHD have been partially successful however increasing antibiotic resistance and the realisation that many bacteria have important anti-inflammatory properties severely limits this approach. Thus, identification of important homeostatic regulators of gut integrity and unique pathogenic and protective bacteria represents a critical pathway to improving transplant outcome. We have detected dramatic perturbations in the gut bacteria prior and during SCT, with several new uncharacterised species identified that are tightly regulated by cytokines. This project will employ genomic and molecular-based approaches that will complement and extend our current research, providing valuable insights that will guide strategies to manipulate gut bacteria to prevent lethal acute GVHD and improve transplant outcome.
Dr Siok-Keen Tey, QIMR Berghofer Medical Research Institute
Treatment of chronic graft-versus-host disease with regulatory T cell-directed therapy — insights from gene-marking
Bone marrow transplantation is often the only curative option for high risk leukaemia and lymphoma. Its curative potential lies in the ability of the newly acquired donor immune system to eradicate residual cancer cells. However, the donor immune response can also damage recipient tissues in a process known as graft-versus-host disease (GVHD). GVHD can be very difficult to treat and is the main limitation to the wider application of bone marrow transplantation for blood cancers. In this proposal, we will investigate, in a phase I clinical trial, the use of regulatory T cell (Treg) infusion to treat chronic GVHD. Similar studies conducted by others have shown promising results but the findings were inconclusive because it is unclear how much the infused Treg cells add to Tregs already present in the patients. Our study will be unique in the world because we will ‘gene-mark’ the Treg cells before infusion. This allows us to track the fate of the Treg cells after infusion and investigate the means by which their effect can be enhanced, for example, with co-administration of other drugs, such as interleukin-2. Our study will provide important insight on Treg infusion in real life clinical setting and improve the treatment of GVHD amongst leukaemia survivors.
Dr Jyotsna Batra, Queensland University of Technology
Genetic association study of miRSNPs with risk and prognosis of prostate cancer
The most pressing challenge in prostate cancer research is the search for accurate and robust biomarkers that can be used for early diagnosis of the disease and have sufficient discriminatory power to determine which patient will eventually develop an aggressive disease, thus requiring immediate clinical intervention. microRNA (miRNA) are the small non-coding part of the genome, which regulates translation of the genetic code to proteins in our body. It is estimated that ~30 per cent of human genes are under the control of miRNAs, and this estimate is proposed to be even higher in cancer. We hypothesise that genetic variations in miRNA can affect their impact on prostate cancer pathogenesis. In the current project, we will be analysing the association of these miRNA related genetic variations in 100,000 individuals for prostate cancer risk, aggressiveness, and survival. The outcomes of this study will contribute towards the establishment of miRNA related genetic variations as blood based non-invasive clinical biomarkers of prostate cancer.
Prof Alpha Yap, The University of Queensland
Down-regulation of RhoA signalling mediates HGF/MET-induced tumour progression
We are trying to understand how the ecosystem of the cancer cell influences disease outcome. We know that, ultimately, the clinical impact of cancer is determined by the behavior of its constituent cells. What is increasingly apparent is that cancer cell behavior is also conditioned how it interacts with its local microenvironment. This microenvironment includes blood vessels and fibrous proteins, that can be coopted by the cancer for nourishment and invasion. The microenvironment also includes other cells – both other cancer cells and cells from the tissue of origin. This is especially so for cancers that derive from epithelial tissues, such as the breast, colon and lung, which constitute the majority of solid tumors. One mode of communication between these cells occurs through their physical inter-connection, a fundamental feature of epithelial tissues, that is often preserved as they become cancerous. In particular, recent advances indicate that cells can communicate by exerting mechanical force upon one another, that is sensed by their neighbours.
We aim to identify key molecules that allow HGF to disrupt normal cell-cell communication and promote tumor development. These molecules will constitute potential targets, for new diagnostic tools to characterise disease and prognosis and, ideally, new therapies.
Dr James Wells, The University of Queensland
Memory CD8+ T-cell function in squamous cell carcinoma
Patients receiving organ transplants need to take special medication to stop their bodies from rejecting their new organs. These medications work by suppressing specific elements of their immune systems. A common, unfortunate, and unwanted side effect of these medications is the greatly increased risk of developing a type of skin cancer known as squamous cell carcinoma. In recent years, however, it has become apparent that some medications confer less of a cancer risk whilst still preventing organ rejection, presumably because these medications differ in their mechanism of action. This project aims to understand why some medications confer less of a cancer risk than others by examining specific impacts of different medications on immune system function in a skin cancer model. We will examine whether some medications promote the function of a type of immune cell known as a memory CD8+ T-cell within SCC. To do this we will use an innovative new automated quantitative pathology imaging platform that will allow us to quantify CD8 T-cell subsets and associated effector cytokine release in situ. Our findings will have fundamental implications for our understanding of how to prevent skin cancer development while at the same time preventing organ rejection.
A/Prof Kiarash Khosrotehrani, The University of Queensland
Predictors of mortality in thin melanomas
Melanoma can be a fatal disease depending on the thickness of the tumour at the time of diagnosis. Even among patients with thin melanomas that represent the largest numbers, the disease can result in mortality. Thus, currently a significant proportion of patients who die from melanoma had a thin tumour. Our project proposes to identify factors that can predict which patients will succumb to their disease in this largest category of melanoma patients.
Dr Graham Leggatt, The University of Queensland
Local targeting of immunomodulatory molecules on CD8 T cells in non-melanoma skin cancer
Non-melanoma skin cancers are the most commonly diagnosed cancers in Australia, particularly for sun-exposed individuals in Queensland, and a large financial burden on the Australian health care system. Commonly, these cancers are removed by surgical excision but this can lead to unwanted scarring in regions such as the head and neck. Non-melanoma skin cancers also have the ability to evade our natural immune response and consequently, effective vaccines and immunotherapies are not yet available for these cancers. Our study will look at local delivery of drugs (antibodies) to restore the anti-tumour immune response, thus providing an additional treatment option for patients.
2016 – 2017
Dr Fares Al-Ejeh, QIMR Berghofer Medical Research Institute
The MEK5-ERK5 pathway in triple negative breast cancer: progression and therapy
We identified proteins that are activated in aggressive forms of breast cancer and that this activation leads to reduced survival and less response of patients to treatments. In this project, we will first confirm our findings in a clinically meaningful manner and develop treatment strategies to switch this pathway off in order to improve the survival of women affected by aggressive breast cancers.
Prof Lisa Chopin, Queensland University of Technology
The ghrelin receptor antisense long non-coding RNA, GHSROS, as a potential target for prostate cancer therapy
Prostate cancer is the most commonly diagnosed cancer in Australian men and is a major cause or death and illness. We have discovered a new gene in prostate cancer that plays a role in regulating a large number of other genes in this disease. This gene stimulates processes related to the progression of prostate cancer and prostate tumour growth. We have developed a method to prevent this gene from acting and this might be a useful additional therapy for prostate cancer.
Prof Judith Clements, Queensland University of Technology
Targeting kallikrein proteases to improve treatment options for ovarian cancer
Each year >1,200 Australian women are diagnosed with ovarian cancer of which serous cancer is the most lethal type. Several lines of evidence implicate the kallikrein7(KLK7) protease in contributing to the spread of this cancer. We propose to identify the manner in which KLK7 promotes the spreading within the abdomen and use our in house designed KLK7 inhibitors to determine the potential of KLK7 as a therapeutic target and/or prognostic biomarker for this most lethal cancer.
Dr Bryan Day, QIMR Berghofer Medical Research Institute
Advancing a novel therapy to target brain cancer stem cells
The therapeutic drug salinomycin has recently shown effectiveness against breast cancer stem cells. Our research has discovered that salinomycin may also have positive effects in brain cancer by targeting the tumour propagating or stem cells responsible for tumour formation and further help sensitize brain cancers to chemotherapy and radiation. We aim to further explore the role of salinomycin and develop 2nd generation forms of salinomycin to validate in brain cancer animal models.
Dr Eloise Dray, Queensland University of Technology
Deciphering the role of the protein phosphatase EYA4 in genomic maintenance and breast cancer avoidance
Essential cellular events such as cell growth, repair of DNA damages, or protein-protein interactions are dependent on protein modifications. We propose here to analyse one essential player of these modifications: the protein phosphatase EYA4. EYA4 is a development gene but we recently discovered that it is also essential for DNA damage repair and that EYA4 is over-expressed in breast cancer samples. We will investigate EYA4 function and establish whether it could be used as a novel drug target.
Dr Stacey Edwards, QIMR Berghofer Medical Research Institute
Identifying new breast cancer genes from GWAS
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known genes, suggesting that regulatory DNA sequences are responsible for the associated risk. In this proposal we will identify and characterise these DNA sequences. Understanding how DNA sequence variations contribute to breast cancer will provide new avenues for therapy and preventative measures.
Dr Mathias Francois, University of Queensland
SOX18-VEGF cross-regulation during angiogenesis and blood vascular development
Development of the blood vasculature is essential for embryonic growth and foetal implantation. This biological process also plays a pivotal role in diseases such as cancers, wound healing, stroke, or tissue regeneration. The focus of this research is to delineate at a molecular level how gene expression is coordinated to instruct the formation of the blood vasculature. These molecular events are likely to be recapitulated in diseasestimulated angiogenesis such as eye disorders or ocular injury.
Dr Kate Gartlan, QIMR Berghofer Medical Research Institute
RORƴt inhibition as a novel therapeutic for the prevention of graft-versus-host disease after allogeneic stem cell transplantation
For many Leukaemia patients the only curative treatment is donor stem cell transplantation, however complications arise in most recipients (>50%) due to graft-versus-host disease (GVHD). We have identified a donor cell differentiation program (Th17/Tc17) that exacerbates chronic GVHD without contributing to leukaemia clearance. This study will assess the therapeutic potential of a novel inhibitor that targets the key protein (RORγt), which controls this inflammatory pathway.
Prof Rajiv Khanna, QIMR Berghofer Medical Research Institute
Impact of immune contexture on clinical outcome of adoptive immunotherapy
Cancer cells can hide from the immune system through an intricate network of non-malignant cells which can either prevent access of killer T cells to cancer cells or express immunosuppressive molecules which can attract wrong type of immune cells. Our group has developed killer T cell-based immunotherapy which has shown some promising results in some patients. In this project we are aiming to delineate potential link between tumour microenvironment and effectiveness of immunotherapy.
Prof George Muscat, University of Queensland
Elucidating the role of the nuclear hormone receptor RORƴ1 in breast cancer
Breast cancer develops in 2 phases: firstly as the primary tumor develops, prompting the diagnosis, and secondly if the cancer metastasizes into a different tissue. Our previous studies indicate increased expression of a nuclear receptor, RORγ (a druggable protein) increases the proabaility of metastasis free survival. The project aims at understanding how RORγ exerts its anti-cancer function in cells, and the effect of RORγ drugs on the onset/incidence and growth of cancer in animal models.
Dr Dominic Ng, University of Queensland
Mitotic spindle regulation by a novel Aurora A control mechanism
A cell dividing to generate two daughters (mitosis) is essential for growth and error-free inheritance of DNA. Human mutations associated with mitotic errors causes cancer or congenital defects (eg. dwarfism and microcephaly). Our study of human mutations led to the identification of new proteins required for normal division. In this study, we will determine how these proteins work at the biochemical level to reveal new ways to target cancer or correct division defects for normal growth.
Dr Michael Piper, University of Queensland
Regulation of stem cell differentiation during cerebella development and medulloblastoma
Medulloblastoma (MB), a cerebellar tumour, is the most common childhood cancer of the brain. It arises from the unrestrained growth of neural stem cells, but our understanding of how MB forms is limited. We have identified a protein, Nfix, that is crucial for neural stem cell differentiation during development, and that is misregulated in MB. Here we aim to understand how Nfix mediates cerebellar development, and to apply these findings to reveal the cause of this devastating cancer.
Prof Mark Smyth, QIMR Berghofer Medical Research Institute
Checkpoint blockade and denosumab in the treatment of established primary and metastatic cancers
We have discovered that two drugs that are currently independently used in the clinical management of advanced cancer appear to have a surprising combination benefit against primary tumor growth and spread. This project focuses on their application in melanoma and prostate cancer with a view to understand why they are effective together and how this information can be used to shape the broader use of these and similar types of drugs in this class in combination in advanced cancer patients.
Associate Prof Raymond Steptoe, University of Queensland
Does lymphoma avoid immune destruction by inducing T-cell tolerance?
Lymphoma develops from uncontrolled growth of a sub-type of immune cell, is the most common blood cancer in Australia and is difficult to treat. Lymphoma may be so aggressive because B cells, from which the tumour arises, could disable immune cells (T cells) that would normally prevent tumour growth. We will examine the function of tumour-attacking T cells to determine whether they have been disabled by the tumour. Outcomes will guide future development of treatments for lymphoma.
Associate Prof Vicki Whitehall, QIMR Berghofer Medical Research Institute
Sessile serrated adenoma prevention in a preclinical study
This study will investigate a new type of bowel polyp called a sessile serrated adenoma. We aim to better understand the gene changes that cause these polyps to grow and will test a number of drugs which may help prevent them.