CCWA Research Fellowships
- Clin/A/Prof Nicholas Gottardo
- A/Prof Georgia Halkett
- Dr Juliana Hamzah
- Dr Willem Lesterhuis
- A/Prof Steven Mutsaers
- A/Prof Oliver Rackham
- Dr Jason Waithman
- Dr Vincent Wallace
|Project||Improving the cure rates for the childhood brain cancer, medulloblastoma|
|Fellow||Clin/A/Prof Nicholas Gottardo|
|Institution||Telethon Kids Institute|
This project is focused on medulloblastoma (MB), the most common malignant childhood brain cancer, which accounts for 1 in 5 brain tumours. Current treatment consists of surgery to remove as much of the tumour as is safely possible, followed by radiotherapy (high-energy x-rays) and chemotherapy (anti-cancer medication). The exception to this is infants where radiotherapy is avoided due to the damage it causes to the developing brain. Using these approaches approximately 70% of children in developed countries can be cured; however, long-term treatment-related health problems continue to be a major issue for survivors, significantly impacting upon their quality of life.
New therapeutic interventions are sorely needed in the clinic for these patients. Currently, only a handful of chemotherapies are used worldwide for the treatment of MB, highlighting the need to identify additional effective drugs for this disease. To address this, our laboratory has devised a drug discovery and research strategy to identify and evaluate new drugs to treat MB. This workflow includes using robotics to screen thousands of drugs for their ability to kill MB cells in vitro (in test tubes), then prioritising the drugs found to enhance the activity of the chemotherapeutics currently used in the clinic, to treat children with MB. The efficacy of the best drug combinations are then tested in vivo (in a living organism) in our “clinic of mice”, which are unique mouse models we have established that represent a range of different human MBs.
Chemotherapy for MB principally works by damaging the DNA of cancer cells but these cells also have repair mechanisms that impede the effectiveness of treatment. One of the most promising drugs we identified in our work blocks the DNA damage repair system (a class of drugs known as CHK inhibitors) and thus enhances the effect of chemotherapy. This research aims to further validate CHK inhibitors as promising new treatments for MB. This work will identify the best CHK inhibitor to take into the clinic with the potential long term benefit to cure more children with MB.
|Funding from CCWA||$100,000 for 2018 (($400,000 total, 2016-2019)|
|Fully supported||In the name of Jill Tilly|
|Project||Improving psychosocial support and education for patients diagnosed with brain or head and neck cancer and their carers
|Fellow||A/Prof Georgia Halkett|
Being diagnosed with brain or head and neck cancer is distressing as it is often life threatening has a large impact on people physically and/or mentally. Hence, it is essential that education and support programs are developed and tested to reduce distress and unmet needs for people diagnosed with these cancers and their carers.
Two programs have been developed:
1. RT Prepare program: This program focuses on preparing people for radiotherapy. Little research has been conducted in this area. This teams work in preparing people diagnosed with breast cancer for radiotherapy is recognised internationally; however, this program needs to be refined for people with other cancers. Receiving radiotherapy for brain cancer or head and neck cancer may cause distress due to the head mask they must wear to stop them moving and side effects they might experience. People receiving radiotherapy for head and neck cancer are at risk of severe skin reactions, dry mouth, oral discomfort, mouth ulcers, infections, difficulty chewing and swallowing, impaired taste and extreme weight loss. People receiving radiotherapy for brain cancer may fear side effects such as headaches, hair loss, nausea, extreme tiredness, hearing loss, skin changes, speech difficulties and seizures. Education and support provided by the radiotherapy team before treatment is likely to reduce their anxiety and help them manage side effects.
Research methods for this program will include interviews, development and testing of the education packages and a large scale clinical trial. Main outcomes will include anxiety and distress, concerns and knowledge about radiotherapy and how prepared they feel for treatment.
2. Carer’s Education and Support Program: This program focuses on improving carer’s confidence to look after their loved one after a cancer diagnosis and reducing their level of distress. This research focuses on carers of patients diagnosed with brain cancer or head and neck cancer because these groups would benefit most from extra support. If carers are unable to support their loved one, it is likely that the person with cancer may need additional emergency room visits or hospital admissions. During the program a nurse conducts a telephone assessment, visits the carer at home, provides an individualised resource manual and regular telephone follow-up for 12 months. This program is currently being tested in a randomised controlled trial with carers of people with brain cancer. It needs to be adapted and tested for carers of people with head and neck cancer.
Research into these two programs is essential to improve the education and support provided to individuals and their carers following a diagnosis with either brain cancer or head and neck cancer. The team will also determine the cost of providing these programs and the impact they have on overall healthcare costs.
|Funding from CCWA||$115,000 for 2018 ($460,000 for 2017-2020)|
In the names of Friends of Cancer Council WA, Curtin University Community & the Estate of Violet Sands
|Project||Improving detection and therapy in treatment-resistant cancers
|Fellow||Dr Juliana Hamzah|
|Institution||Harry Perkins Institute of Medical Research|
This research program will potentially benefit patients suffering from treatment-resistant cancers such as triple negative breast cancer and liver cancers. Approximately one in eight Australian women will be diagnosed with breast cancer before the age of 85. Similarly, liver cancer is the third leading cause of death in Australia. Treatment options that include conventional chemotherapeutics are currently ineffective.
Dr Hamzah has identified tumour stiffness as the major problem in breast and liver cancers. Tumour stiffness is caused by over-production of non-cellular matrix components that protects the tumour cells from being accessible to anti-cancer drugs. Consequently, the stiffer the tumour matrix, the more resistant it is to drug therapy. Recently this team has developed a new medication and treatment to specifically dissolve tumour stiffness. Degradation of matrix stiffness effectively exposes the tumour cells to anti-cancer medications. Dr Hamzah’s goal is to explore the use of this drug to treat breast and liver cancers.
|Funding from CCWA||$120,000 for 2018 ($480,000 for 2018-2021)|
In the names of the Estate of Paulus Hoogenduk, Jackson McDonald & the Estate of Donald Weall
|Project||Identifyng new effective treatments for mesothelioma|
|Fellow||Dr Willem Lesterhuis|
|Institution||The University of Western Australia|
This research focuses on mesothelioma, a fatal cancer of the lining of the lung, caused by exposure to asbestos. Western Australia has the highest incidence of this cancer in the world, because of the mining, transport and high use of asbestos here.
Chemotherapy has some effect in a number of patients, but always short-lived. Immunotherapy, which boosts the immune system against cancer, appears promising with some patients showing a remarkable decrease in cancer burden, but unfortunately this does not happen very often. The outcome for people with mesothelioma has not improved in more than a decade.
Firstly, the intention is to investigate whether chemotherapy and immunotherapy are more effective when they are used in combination. The idea has always been that chemotherapy has only harmful effects on the immune system, but research shows that some of these drugs may actually have beneficial effects. However, it’s not known which chemotherapeutics can be best combined with immunotherapy. Here, the intention is to test all different classes of cancer chemotherapy for their ability to work in combination with immunotherapy, and study the mechanisms that determine the combined anti-cancer effect.
Secondly, the intention is to investigate why some people with cancer who are treated with immunotherapy have a full regression of their cancer, while others have no response to the therapy at all. By investigating which cells and molecules are responsible for the anti-cancer effect, and by subsequently reinforcing those processes using already available drugs, The aim to increase the cure rate.
Lastly, the intention is to investigate which cells and molecules are involved in the fast growth of mesothelioma, and to aim to identify drugs that stop this process.
This will be conducted using mesothelioma animal models, and samples from mesothelioma patients. Since many of the drugs tested are already in clinical use, the findings can be rapidly translated into the clinic; for some of the drugs this may be within 5 years.
|Funding from CCWA||$20,000 for 2018 ($80,000 in total for 2017-2020)|
|Fully supported||In the name of Australia Post
|Project||Small non-coding RNAs in malignant mesothelioma|
|Fellow||A/Prof Steven Mutsaers|
|Institution||Institute for Respiratory Health|
This project explores the potential for microRNAs, small fragments of genetic material, as novel diagnostic, early disease and prognostic markers in malignant mesothelioma (MM). Currently, diagnosis of MM is difficult and may take up to 3 months which can impact on patient treatment. By investigating these molecules in clinical samples from patients, this project hopes to develop biomarkers for early diagnosis and identify those patients with better disease outcomes. It will also investigate the biological role of these molecules in MM to identify novel molecules as therapeutic targets to treat this disease.
|Funding from CCWA||$40,000 ($320,000 total for 2013-2014 and 2017-2018)|
|Fully supported||In the name of the Estate of Violet Sands|
|Project||Correcting gene expression in pancreatic cancer
|Fellow||A/Prof Oliver Rackham|
|Institution||Harry Perkins Institute of Medical Research
Normal genes responsible for cell growth, development, and differentiation can cause cancer when their activity or expression is increased, so called "oncogenes". Other genes that normally act to stop the uncontrolled growth of cells - "tumour suppressor" genes - can also cause cancer if mutations or reduced gene expression lower their activity. Therefore, cancer is fundamentally a disease of defective genes and gene expression. This project will use cutting edge synthetic biology approaches to create new technologies to control gene expression, providing new ways to understand cancer targets and new protein-based therapies to modulate gene expression in cancers that resist current treatment regimes.
|Funding from CCWA||$100,000 for 2018 ($400,000 in total for 2015-2018)|
In the names of Charles Lockwood, in memory of Rosemary Hale & the Estate of Paulus Hoogendyk
|Project||Empowering the immune system to attack melanoma and other advanced cancers
|Fellow||Dr Jason Waithman|
|Institution||Telethon Kids Institute|
Melanoma is Australia’s 3rd most common cancer resulting in the 9th highest number of cancer-related deaths. There is traditionally poor prognosis once it spreads. New treatments that harness the immune system can cure many people with advanced melanoma. However, there is urgent need to help patients that aren’t responding to these immunotherapies. To address this, the research strategy focuses on the following aims: to improve the body’s immune system to fight cancer and thereby increase the number of patients surviving; to help the immune system to better detect and attack cancer cells, which leads to saving lives; to understand how the immune system can be improved to stop the spread of melanoma cancer in the brain - this is critical as it is a very poor prognosis once in the brain; and to understand how specific immune cells might offer protection from skin cancer and keep tumours dormant, thereby directly saving lives.
The purpose of this research is to gain more insight into how the immune system interacts with cancer cells and develop new ways to make the immune system fight cancer. To do this the research work focuses on T cells, which recognise and marshal an attack against diseased cells. The team are engineering T cells with additional capabilities, making them more able to eradicate tumour cells. They are also generating a vaccine that causes T cells to multiply so they can overwhelm cancer cells and eliminate them.
As melanoma frequently spreads to the brain the team are also investigating how an immune response is directed against tumours within the brain and testing whether the new therapies are effective.
Also, tumours can remain dormant for prolonged periods of time and patients can live normally. Little is known about how this occurs. The team will identify the role of the immune system in tumour dormancy, which will lead to new therapeutic approaches that convert aggressive cancer into a stable chronic condition.
Through this work the intention is to identify multiple ways to drive and enhance T cell immunity against cancer. This research will save lives by improving the overall survival rate, especially in patients currently deemed terminal and non-responsive to immunotherapy.
|Funding from CCWA||$120,000 in 2018 ($480,000 total for 2018-2021)|
|Fully supported||In the name of the Rosemary Grant Zaks Melanoma Research Fellowship|
|Project||Improving breast cancer surgery with a tool that helps the surgeon remove all of the tumour in one go
|Fellow||Dr Vincent Wallace|
|Institution||The University of Western Australia
This study will develop and test a surgical tool that uses a new technology, known as terahertz technology, to help surgeons remove cancer. Every year, approximately 3,000 breast cancer patients in Australia will require a second surgical procedure because not all of the cancer has been removed during their first surgery. This is because it is difficult for surgeons to identify where the cancer starts and the healthy tissue begins so they can remove all of the tumour in one go. There is a real need for an accurate, real-time, non-destructive way to assess tumour margins (the boundary between tumours and healthy tissue) during surgery.
|Funding from CCWA||$100,000 for 2018 ($428,000in total for 2015-2018)|
|Fully supported||In the name of The Youngberg Women’s Cancer Research Fellowship|