Blood Cancer Research Programs
Biological Characterisation and Therapeutic Options for High Risk, DDX41 Mutated, Haematological Malignancies
Dr Anna Brown; University of South Australia
Leukaemia is the eighth most commonly diagnosed cancer in South Australians, with some families carrying genetic changes that greatly increase their risk of developing blood cancers such as leukaemia.
Using DNA sequencing technologies, we have identified causal gene mutations in a gene called DDX41 which can cause leukaemia. Through your support, we will investigate the function of DDX41 in blood cells to determine how it works normally and how it causes leukaemia. We also hope to identify news targets for treating blood cancers with mutations in DDX41, which will ultimately transform how this type of cancer is treated.
Therapeutic Targeting of Cancer Dissemination in Multiple Myeloma to Prevent Disease Progression and Relapse
Dr Kate VanDyke; University of Adelaide
Multiple myeloma (MM) is an incurable haematological cancer that is responsible for an estimated 80,000 deaths every year worldwide. Even with the best available current therapies, almost all MM patients eventually relapse, with only 15 per cent of patients surviving 10 years from diagnosis. Previous studies have identified that those patients that have highly ‘metastatic’ MM tumour cells at diagnosis do particularly poorly, leading to rapid disease progression, relapse after treatment and death. Identification of the factor(s) involved in the recirculation and dissemination process in MM is therefore key in the development of therapeutic strategies that will prevent relapse in these patients.
Through your support, we will investigate why some patients do very poorly after diagnosis (surviving less than two years) and identify tailored treatments for this group. Importantly, our work focuses on the repurposing of existing targeted therapies that have been trialled in other disease settings. This makes translation of the results of these studies to the clinic feasible in the short term, meaning that real improvements in survival outcomes should be rapid for these patients who traditionally have had very poor outcomes.
Both the University of Adelaide and SAHMRI have a critical need to expand bioinformatics services to health and biomedical researchers now based at the west-end precinct, and also to the North Terrace and Waite campuses of the University. Under a new joint initiative these two research entities have agreed upon a joint vision to achieve this need moving forward.
Through your support, we will be able to fund the appointment of a junior Bioinformatician for a period of three years. SAHMRI Cancer Theme will position their Leukaemia Bioinformatician within this core, as well as establish a new position for a Bioinformatician in the specialty area of Epigenetics and broader Cancer Genomics.
This position will work closely with the SAHMRI Cancer Theme, within the SAHMRI David Gunn Genomics Facility and will provide services across the precinct in these areas, adding value to the whole research community of South Australia.
Acute Lymphoblastic Leukaemia (ALL) is the most common childhood cancer and remains the leading cause of non-traumatic death in children. Adolescents and young adults with ALL have poor therapeutic outcomes and most adults will die of their disease.
Genomic analysis has revealed several new, high-risk ALL lesions that may be targetable with rational therapies. This is supported by anecdotal reports of significantly improved outcomes, but to date both druggable target identification and patient access to these therapies is limited. Importantly, patients with high risk genomic lesions are currently not recognised at diagnosis and are only screened for genomic lesions when they relapse or fail to respond to chemotherapy; for many patients this is too late. They then undergo high dose toxic chemotherapy and/or transplantation, both associated with life-long risk of co-morbidities and second malignancy. Newer immune based therapies are emerging, but we currently don't know which patients will benefit from these approaches.
Through your support we will investigate Precision Medicine, integrating genomics, metagenomics, bioinformatics and functional analyses, to provide diagnostic screening and therapeutic triage models that are readily accessible and importantly, will transform treatment and outcomes for our most vulnerable ALL patients. Our group is ideally placed to bring real change for ALL patients to ensure they receive the right therapeutic approach early, improving the clinical outcomes for patients with ALL, which can then extend to other cancers.
Preclinical Modelling of T-Cell Acute Lymphoblastic Leukaemia: Defining Targeted Therapies and Preventing Treatment Resistance
Dr Laura Eadie; SAHMRI
T-cell Acute Lymphoblastic Leukaemia (T-ALL) is a genetically complex high-risk disease affecting children and adults, with novel treatments urgently required. T-ALL is diagnosed at a rate of 60 patients per year in Australia, most commonly affecting children 0–14 years old (60 per cent of all T-ALL cases) and is universally treated with high dose, multi-agent chemotherapy.
While effective, these treatments can result in toxicity and long-term side effects. In addition, the primary clinical issue in ALL is treatment resistance, with 25 per cent of paediatric T-ALL patients at risk of primary resistance (leukemic induction failure) or relapse. The outlook is worse for adult T-ALL patients, with 40 per cent of patients failing therapy.
Through your support, we will assess targeted therapies in mouse models of T-ALL through ongoing generation of 1) patient derived xenograft models from all T-ALL samples received in our laboratory and 2) production of transgenic models of T-ALL.
This will enable the evaluation of novel and combination therapeutic approaches compared with the current standard of care. Because it is expected some of these cases will develop therapy resistance, mouse models of drug resistance will also be developed and pre-emptive intervention in the resistant disease setting investigated.
Towards a New Genomic Classification of Risk for Patients with Chronic Myeloid Leukaemia
Associate Professor Susan Branford; University of South Australia
Survival for patients with chronic myeloid leukaemia has improved; however, a proportion still fail therapy. Failure is related to poorly defined genetic abnormalities that may already be present at diagnosis.
Through your support, we will be able to detect these abnormalities using state-of-the art sequencing technologies and develop new ways to stratify patients at diagnosis according to their risk of treatment failure.
Germline and Somatic Genetic Variation in Cancer
Professor Hamish Scott; University of South Australia
All diseases in humans have a genetic component, either inherited or caused by cell mutation. When we first started looking at haematological cancers such as lymphoma and leukaemia, it was thought that genetics didn’t matter. Families with more than one case were just considered ‘unlucky’. Now it is recognised that more than 10 per cent to 20 per cent of these cancers have a strong genetic component.
Through your support, we will be able to work on therapies that can address the genetic implications of some of these cancers, find better ways of treating and monitoring them, and ultimately save lives.
Improving Our Understanding of Cancer Biology, Diagnostics and Therapies
Professor Tim Hughes; University of Adelaide
Just over a decade ago, Chronic Myeloid Leukaemia (CML) was still considered a death sentence. This research has pioneered the use of tyrosine kinase inhibitors (TKIs) to treat a range of cancers including CML, which was once known as one of the most devastating forms of blood cancer. Through the use of TKIs and research into individualised therapies, we have seen significant breakthroughs, with some CML patients even achieving treatment-free cancer remission. This in itself is a remarkable achievement considering that previously, only one in six CML patients survived eight years after their diagnosis.
Thanks to Cancer Council's Beat Cancer Project, our team has received ongoing funding to support our work since 2013. We're currently leading a global trial of a promising new therapy for CML, with results to be released later this year. Funding from the Cancer Council's Beat Cancer Project has enabled our team to lead this and other research projects in South Australia which will ultimately change lives.
Network (SACTN)—Clinical Trial Enhancement/SA Teletrial: Bringing Cancer Clinical Trials to the Country
Dr Dagmara Poprawski; Country Health SA
There are currently no cancer clinical trials offered outside of metropolitan Adelaide, meaning that patients from regional areas are required to travel in order to take part. The benefits of cancer patients participating in clinical trials are well recognised, particularly the ability to increase patient access to a full suite of therapy options including novel therapies.
Through your support, we will be able to look at the best way for patients in the South East to be recruited, treated and attend follow-up visits virtually from Mt Gambier hospital directly to sites like Flinders Medical Centre. This Teletrial model will utilise existing services, along with additional resources funded through this application, to establish regional cancer trial sites in the long term.
Even though we're at early stages, our hope is that the tele-clinical trial model will improve trial participation rates in non-metropolitan areas and ultimately, improve patient care.
Improving the Management of Chemotherapy-Induced Nausea by Assessing and Treating Nausea as a Symptom Cluster
Professor Ian Olver; University of Adelaide
Current drug therapies can successfully prevent vomiting after chemotherapy; however, the majority of patients who undergo chemotherapy still suffer some form of nausea. Patients differ in what symptoms they label as nausea, all of which may need separate treatment.
Through your support, we will develop an App to find out what symptoms each patient reports as nausea and aim to see if we can improve it by treating each unique symptom. We will also monitor risk factors for nausea to see if we can prevent it occurring before chemotherapy treatment.
Clinical Cancer Registry
Professor Caroline Miller and Professor David Roder; SAHMRI and University of South Australia
The South Australia Clinical Cancer Registry (SACCR) consists of four hospital-based clinical cancer registries and a central coordinating unit. The clinical registries provide information on cancer stage, grade, differentiation, treatments (surgery, radiotherapy, chemotherapy etc.), prognostic indicators, patient outcomes and other key indicators of quality cancer care that are needed to complement population incidence registries.
Data is limited to those who are treated at participating hospitals Flinders Medical Centre, The Queen Elizabeth Hospital, Lyell McEwin Health Service and the Royal Adelaide Hospital. Clinical registries provide clinicians and service planners with appropriate insight into current cancer trends and the impacts of changes to clinical practice and models of care on outcomes. There are over 300 data items potentially collected as defined by the South Australian minimum data set.
With the funding received through Cancer Council’s Beat Cancer Project and other revenues, we will be able to continue collecting South Australian cancer-related data, enabling effective public health interventions and cancer incidence monitoring through sharing this data with clinicians and service planners.
My wife succumbed to breast cancer when aged 40. During the 15 months she lived with cancer, she experienced major drug toxicities and many ineffective drug treatments, many of which could have been avoided with better utilisation of biological markers and a higher level of pharmaceutical care. Her experience motivated me to optimise drug treatments for future generations, ensuring that others don’t have to experience what she went through.
The ongoing support of Cancer Council’s Beat Cancer Project will help us develop better and more effective drugs to treat cancer. We are researching across three main areas: using Indigenous knowledge and Australia's remarkable marine biodiversity to identify new compounds with therapeutic potential in cancer and related conditions; using sophisticated statistical methods to determine if such biomarkers (biological indicators of disease) will be useful decision tools in cancer therapy; and studying the mechanisms by which cancer drugs are metabolised to determine ways to optimise drug strategies.
My message to donors is that drug discovery is difficult and challenging, but through a continuity of funding, we are getting closer to drug breakthroughs every day.
The primary aim of our unit is to develop more efficient and cost-effective services, especially related to cancer screening and treatment. With cancer impacting one in two Australians by the time they turn 85, our work is to benefit the whole Australian population, with the funding we receive from Cancer Council SA greatly increasing the reach of our work.
Through your support, our next step is to assist in the implementation of evidence-based health policies and evaluate their effectiveness. This work is ongoing, with a major emphasis on evaluating and improving outcomes of services for Aboriginal people. We are also working on assessing side effects of cancer therapies in order to improve the quality of life for those who survive their cancer diagnosis, and looking at service evaluation and policy development for breast and cervical screening and cancer treatment services.
South Australia has a range of data sets across health, education and social services. Once linked, data describing the health and experience of many thousands of individuals can be supplied to a researcher in a completely de-identified format. This intelligent linkage process strengthens privacy protection while giving researchers access to true population-based data relevant to many areas of research, including cancer prevalence, detection, treatment and outcomes.
Through your support, SANT DataLink is committed to contributing to a better understanding of cancer prevalence, factors contributing to this and improved treatments and outcomes for the community and individuals.
Immunotherapies that stimulate the immune system to attack and kill tumours represent an exciting new era in cancer treatment. The immune system contains cells that have the unique capacity to destroy cancer; however, tumours often develop ways to ‘turn off’ these cells and escape destruction. The most successful new immunotherapies work by blocking the tumour's method of escaping and allowing the immune system to kill cancerous cells. These therapies can be highly effective in solid tumours such as melanoma, with around 40 per cent of melanoma patients responding to therapy and some patients achieving a complete response where their tumours are eradicated. Despite these successes, approximately 60 per cent of melanoma patients do not respond. Other forms of solid cancers like brain cancers also fail to respond, and so these patients are completely missing out on these breakthrough treatments.
Through the support of Cancer Council's Beat Cancer Project, we plan to extend the promise of immunotherapy to all patients. We’re testing brand new immune-based therapies specifically designed to boost the immune system in solid cancer patients. We have one clinical trial currently running at the Royal Adelaide Hospital which tests a personalised cell therapy in patients with melanoma. We will soon commence two new cell therapy clinical trials in patients with brain cancer. This project will help develop these trials and also follow patients receiving the new treatment to see how they respond, with the hope that the results can help inform treatments for all patients diagnosed with solid tumours.
The ACRF Centre for Integrated Cancer Systems Biology (ACRF-CICSB) will be a state-of-the art facility providing new approaches to interrogate cancer biology. This facility will be located at SAHMRI and the University of Adelaide’s newly constructed Adelaide Health and Medical Sciences (AHMS) Building (located adjacent to SAHMRI), in the newly established Adelaide BioMed City (ABMC) precinct.
South Australia has a strong national and international reputation for undertaking high quality research in cancer biology and treatment. Our translationally-focused research teams are already well supported by well-established enabling facilities located throughout Adelaide. Collectively, these facilities underpin many of the outstanding research discoveries from South Australian cancer researchers focused on understanding the intrinsic and extrinsic mechanisms of cancer initiation and progression, drug sensitivity and resistance and the mechanisms of cancer metastasis.
A data officer to support the familial cancer research of the Adult Genetics Unit
Dr Nicola Poplawski; CALHN
This application is for a three year salary for a 0.6 FTE ASO2 data officer to assist in the data management of the Adult Genetics Unit's KinTrak family database, improving the the opportunities for SA families to participate in familial cancer research.
When a client is referred to the AGU we collect and record family history information. The data is collated in KinTrak and clinical staff use the information to determine which cancer genes will be tested and provide an assessment of personal cancer risk.
If a genetic error is identified in a cancer gene, clinical staff use the information to manage risk notification and predictive genetic testing for current and future generations of the family; ensure relatives who do not have the genetic error avoid unnecessary cancer surveillance and provide relatives who do have the genetic error with gene specific risk management advice that lowers their cancer risk (prevention and risk reduction) and enhances detection of early stage cancer (surveillance).
Where ethically approved, research staff use the information to identify individuals/families who are eligible for recruitment to familial cancer research projects; identify individuals/families who are eligible for research or translational genetic testing and contribute data to local, national and international research initiatives relevant to familial cancer
Through support from Cancer Council’s Beat Cancer Project we will be able to employ a data officer to take over these tasks and also support and contribute to AGU research activity; freeing clinical staff for research activities.
In addition to funding individual research projects, Cancer Council’s Beat Cancer Project is proud to fund a number of travel grants, awarded to South Australian researchers across all the major research institutions. Funded through your generous donations, these grants help cover costs for researchers to travel to local, national and international events and conferences. It also gives them an opportunity to talk about their research with other experts, helping them to broaden their skills and learn from leading researchers.
Cancer Council SA’s Behavioural Research Team is based at our offices at Greenhill Road. Through your support, the team conducts monitoring, applied research and evaluation to inform the development of Cancer Council SA's cancer control programs and services. The Behavioural Research Team works closely with the Cancer Council SA Postdoctoral Fellow (Cancer Support) who is jointly based at the Flinders Centre for Innovation in Cancer. Together with two new postgraduate research students from Flinders University, they are interested in people’s knowledge, attitude, behaviours and the decisions individuals make that may lead to healthy or unhealthy behaviours in the area of cancer control, as well as research into the psychosocial impact of cancer on those directly and indirectly affected by cancer.