“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.
You can read about our recently awarded cancer research grants below.
Accelerating Collaborative Cancer Research (ACCR) Grants
The following Accelerating Collaborative Cancer Research Grants have been awarded in honour of Don and Ray Paech and their philanthropic contribution to Cancer Council Queensland.
Lead Investigator: Professor Penelope Webb
Administering Institution: QIMR Berghofer Medical Research Institute
Project Title: PROMISE: Patient-Reported Outcome Measures in cancer care: a hybrid effectiveness-Implementation trial to optimise Symptom control and health service Experience
In Queensland there were more than 280,000 cancer survivors in 2015; nationally the total is expected to reach 1.4 million by 2020. It is thus important we care for those affected in the most cost-effective way. Two recent trials found cancer patients who completed regular on-line questionnaires (electronic patient-reported-outcome-measures, e-PROMs) to tell their healthcare team how they were feeling, had better quality of life and significantly better survival than those receiving usual care. However, other studies have reported more modest benefits. As these systems are being introduced into clinical practice, it is important they are tested to ensure they are both effective and cost-effective in the Australian setting. We propose a randomised trial to test the effectiveness and cost-effectiveness of the use of ePROM tools in routine cancer care to improve patient outcomes. If the tools are effective, this would lead to improved quality of life for cancer patients and lower mortality rates. They would particularly benefit those in rural/remote areas who have to travel to major centres for follow-up. It will also support adaptation of the tools, co-designed with specific cultural populations to ensure relevance, further optimise access and ensure equality for all Queenslanders with cancer.
Lead Investigator: Professor Mark Smyth
Administering Institution: QIMR Berghofer Medical Research Institute
Project Title: LUCKI STARS: Lung cancer knowledge in immunogenomics to stratify therapeutic resistance and sensitivity
LUCKI STARS (Lung cancer knowledge in immunogenomics to stratify therapeutic resistance and sensitivity) is a new 11-member multi-disciplinary research network dedicated to developing diagnostic tools and therapeutic interventions to improve our understanding of lung cancer patient response or resistance to immunotherapy. Immunotherapy describes a collection of biological agents that boost the patient’s immune system to fight disease. These therapies work very well in some lung cancer patients, but not others. The team wants to know why this is and how to make this strategy effective for every patient. The team comprises cross disciplinary expertise including clinical care of lung cancer, and research experts in genomics, immunology and detection/prognostic biomarkers. Lung cancer is a major killer and key unmet clinical needs are to: 1) understand lung cancer patient response and resistance to current immunotherapy; 2) develop biomarkers of lung cancer response and resistance; and 3) treat lung cancer earlier with new combination immunotherapies. The team will interrogate the best available human lung cancer samples from clinical trial patients pre- and post-treatment. They will be using a variety of cutting-edge, integrated methodological approaches to evaluate the cancer cells and immune cells to improve patients’ response to therapies.
Current Cancer Research Project Grants
2019 – 2020
Dr Bryan Day, QIMR Berghofer Medical Research Institute
Dystroglycan Complex Targeting: A Novel Approach to Eliminate Tumour-Initiating Cells in Adult Brain Cancer
Glioblastomas (GBMs) are the most common and aggressive brain cancers. It is now becoming understood that solid tumours are made of many types of cancerous cells including cancer stem cells. It is thought that these cells are responsible for tumour initiation and recurrence. We have identified a cell receptor termed dystroglycan, which keeps brain cancer cells in an aggressive state. We are now investigating approaches to target this receptor to prolong brain cancer patient survival.
Professor Riccardo Dolcetti, The University of Queensland
Strategies to overcome immune-resistance to cancer vaccines
This project seeks to take advantage from our novel, versatile and effective cancer vaccine platform to explore strategies able to overcome two major mechanisms of immune resistance to cancer immunotherapy: the defective ability of some tumours to present antigens to the immune system and the immune suppression induced by excessive inflammation. The full exploitation of the therapeutic potential of our novel cancer vaccine will enhance the applicability and efficacy of cancer immunotherapy.
Associate Professor Juliet French, QIMR Berghofer Medical Research Institute
Combining genetics and genomics to identify multi-cancer risk genes.
Hormone-related cancers represent a major health and economic burden. Collectively, breast, ovarian, endometrial and prostate cancers accounted for more than 28% of all cancers diagnosed in Australia last year. This project will identify the key genes responsible for risk of multiple cancers. These multi-cancer genes may represent novel drug targets that could be used to prevent or treat multiple cancer types.
Professor Nikolas Haass, The University of Queensland
Induction of endoplasmic reticulum stress to potentiate immunogenic cell death to improve melanoma therapy
Utilising unique microscopy techniques, we have demonstrated that bortezomib causes cell stress and subsequent cell death of melanoma cells.
Moreover, our preliminary data demonstrate that treatment with bortezomib results in the upregulation of proteins that mark the melanoma cells for identification by the immune system. We hypothesise that bortezomib can be used as an immunogenic cell death inducer to enhance anti-tumour responses in melanoma.
Dr Brett Hollier, Queensland University of Technology
Targeting the adaptive response to androgen-deprivation as an adjuvant therapy for advanced prostate cancer
Prostate cancer accounts for over 3,000 deaths annually in Australia, which is due to the ability of cancer cells to adapt and survive current treatments. We have identified a protein, Neuropilin-1 (NRP1), which may be involved in this adaptive response to therapy and allow cancer cells to progress to a treatment-resistant state. This study will define the role for NRP1 in tumour progression and test two agents that block NRP1 function as potential novel therapies for advanced prostate cancer.
Professor Kum Kum Khanna, QIMR Berghofer Medical Research Institute
To investigate the mechanistic and functional roles of MLK4 in mediating radio-resistance of breast cancer stem cells
Numbers of studies have suggested the importance of targeting cancer stem cells (CSCs) in patients who suffer a cancer relapse. Our current data suggest that MLK4 is a promising molecular target in mediating changes of CSC populations in response to radiotherapies using ionising radiation. We thus propose to investigate molecular mechanism attributing to the incomplete elimination of CSCs during radiotherapy, establishing a new potential target to overcome cancer relapse.
Professor Gregory Monteith, The University of Queensland
Exploiting remodelling of calcium signalling to specifically target triple negative breast cancer via promotion of apoptosis
Triple negative breast cancers are a type of breast cancer that is still not treated effectively. Women with this disease are more likely to have their breast cancer spread to the lung and the brain. The work in this grant builds on the identification of drug targets that are at high levels in this type of breast cancer. When these drug targets are inhibited, triple negative breast cancer cells are more likely to undergo cell death with exposure to cancer therapies.
Associate Professor Helmut Schaider, The University of Queensland
O-linked-N-acetylglucosamine transferase and ten-eleven translocation 1 facilitate therapy induced cellular reprogramming leading to acquired drug resistance in cancer
Drug resistance is an ever occurring problem for a successful treatment in cancer patients. One of the mechanisms assumed leading to permanent resistance is an adaptive generic process based on a chronic stress response. We have identified two factors involved in this stress response. One can be targeted by small compounds or peptides which will be developed and tested in preclinical models. Inhibition of these factors will allow for improved survival and prolonged remission in cancer patients.
Professor Mark Smyth, QIMR Berghofer Medical Research Institute
Nectin-like molecules in cancer
Immunotherapy is emerging as an alternative to standard anti-cancer therapies, but many patients still do not benefit from these immunotherapies. We have early data to show that a stress-induced molecule, CD155, expressed on immune and tumour cells, promotes tumour growth and spread. We hypothesise CD112 does similar and may act in concert with CD155, to hinder contemporary immunotherapy. We wish to further study these pathways in animal models and responder and non-responder patient samples.
Associate Professor Vicki Whitehall, QIMR Berghofer Medical Research Institute
High Risk Sessile Serrated Adenomas of the Colorectum
Bowel cancer is very common and will be diagnosed in 1/12 Australians living to age 85. Fortunately we can prevent bowel cancer from developing by removing the small growths, called polyps, that precede development of cancer. This application proposes to look at a specific type of bowel polyp called a sessile serrated adenoma, which is difficult to detect and can progress rapidly to cancer. We will develop markers to predict risk of these polyps to inform surveillance guidelines.
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.