2021 successful cancer researchers and projects

This study aims to identify the leukaemia cells that resist treatment and are responsible for relapse, to better track them and discover new methods to destroy them. We will use animal models uniquely available in our lab to reproduce the standard therapy used in clinics and to test new drugs in a preclinical setting. Outcomes from this study are intended to develop new treatments and tools for clinicians to improve the quality of care and long-term survival of all children with leukaemia.

We tested thousands of drugs, known to be safe for people, for their ability to kill MB cells. Over the last few years we have tested the best drugs further and selected the two most promising. We now aim to investigate these drugs in combination with each other and with radiation – a major part of MB treatment.

We mimic human MB in the lab as closely as is currently possible by using gold-standard animal models and use sophisticated equipment to deliver radiation therapy. Our experiments are designed to determine if these drugs can work safely and effectively alongside radiation. In this way, the results can be rapidly translated into the clinical setting to improve survival and benefit children and their families.

Our ultimate research goal is to prevent sarcoma relapse after surgery. We aim to do this by using the wound healing process against the cancer; surgery causes an increased immune response and can expose vulnerabilities in cancer cells. We will use this to our advantage to prevent cancer growing back, to improve outcomes for patients.

We will investigate which genes are switched on in sarcoma following surgery and use computational methods to identify drug targets and currently available drugs to re-purpose. We will then test these drugs in mouse models.

In the future, we aim to develop local therapies for the clinic, which can be applied after surgery to prevent  relapse.

The immune system can fight cancer by eliminating malignant cells or by preventing the growth and spread of cells that escape eradication. We want to understand how the immune system controls tumour growth so we can develop new immunotherapies to eliminate cancer.

We have developed a world first animal model that allows us to examine how the immune system can keep cancer cells in a dormant state. Using this model, we found that specialised immune cells called tissue resident memory T cells, controlled tumour development. Using cutting edge technology, we will investigate how these T cells communicate with other immune cells, and cancer cells, in the skin to prevent melanoma
growth. This will allow us to identify new ways of manipulating immune cells, such as boosting their numbers or their cancer killing activity for more effective treatment of cancer.

This project aims to analyse both UM tumours from the eye and the liver. We will use cutting-edge technology to analyse thousands of the cells that form a tumour, one at a time. The results of this project will aid our understanding of how UM tumour cells behave within the metastases, and how UM cells interact with liver cells to enable the tumour growth. This study is expected to find new ways to treat the disease and prevent the development of metastasis.

Treatment for ALL using chemotherapy has improved significantly in past 50 years and now over 9 out of 10 children with ALL are alive at 5 years from diagnosis, with most cured of their leukaemia. Unfortunately, infants with ALL (iALL) have much poorer survival rates due to early leukaemia relapse.

At Telethon Kids Institute we have identified a class of drugs that is active in iALL that have never been used for treating iALL. Concurrently our local collaborator has produced 10 new drugs in this very same class that has never been tested in cancer. We aim to test these agents together in more detail to determine their effectiveness in treating iALL. We also aim to translate the use of these novel agents into clinical trials and improve the survival rates in iALL.

This study aims to better understand the biology of each patient’s melanoma and identify if the presence of certain DNA modifiers (epigenetic markers) in the blood of patients can be used to predict response to treatment. These signatures can then be developed into a blood test which in turn will allow easy identification of tumours that will respond to immunotherapies or those who may require alternative therapy to ensure an optimal outcome. The outcomes of this study will help clinicians make informed treatment decisions and improve patient outcomes.

Treatment often fails because an ovarian tumour is made up of many different types of cancer cells. Some types of cancer cells may be destroyed by the treatment, while other types turn out to be resistant and allow the tumour to grow further. The research team proposes to investigate the different types of ovarian cancer cells to understand how they are related and why some of them are not killed by the treatment.

A novel technology called spatial transcriptomics will be used, which will allow for the creation of maps of cells in an area of the tumour. Several different areas in each tumour will be mapped and the cancer cells examined. This will enable the comparison of cells and cell interactions in different areas of the tumour.

The findings of this study may be used in the future to make tumours more sensitive to treatment and improve outcomes of women with ovarian cancer. The proposed strategy, once established, can also be applied to many other types of cancer.

Prostate-specific antigen (PSA) is the only screening biomarker for prostate cancer but because it is not always produced by malignant cells, this biomarker is not entirely reliable since it can generate false results. There is an urgent need for identification and validation of biomarkers and prostate cancer genes. Our study will be the first to address both of those needs.

The proposed studies aim to develop tests that can be done from a blood sample. These tests make use of new technologies to test for evidence of markers derived from the growth (tumour) found in the blood of patients with melanoma. These markers could serve as a guide of what is going on in the cancer. A/Prof Gray aims to demonstrate that in melanoma, these tests can effectively and accurately provide the oncologists with information about the growths, for them to take better informed treatment decisions.

1. Radiotherapy Prepare program

This program focuses on preparing people for radiotherapy. Little research has been conducted in this area. This team’s 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 a 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.

Dr Hamzah has identified tumour stiffness as the major problem in breast and liver cancers. Tumour stiffness is caused by the over-production of non-cellular matrix components that protect 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.

This study aims to identify the treatment-resistant cells that are responsible for relapse, and discover new methods to destroy them. The study will use animal models to reproduce the standard therapy used in clinics and add two promising drugs to destroy these cells. The study will also look for agents that improve the efficacy of these two drugs, and extend to non-DS children with leukaemia that have a similar molecular makeup to DS children. Outcomes from this study are to develop new treatments for clinicians to improve the quality of care and long-term survival of West Australian children with leukaemia.

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.

Due to symptoms of fatigue and shortness of breath, people with advanced NSCLC report adopting a sedentary lifestyle. In people with breast cancer, diabetes, heart or lung disease, time spent being physically active during the day is linked with longer survival, whereas prolonged time spent sedentary during the day is linked with shorter survival. Although prolonging survival is the main goal of treatments for people with advanced NSCLC, studies in these people have not yet investigated the link between time spent either physically active or sedentary during the day and survival. So, the aim of this study is to investigate if time spent in physically active or sedentary during the day predicts survival in people with
advanced NSCLC.

The intention is to recruit people diagnosed with advanced NSCLC and ask them to wear a physical activity monitor 24 hours per day for seven days in a row. This monitor will show the amount of time people spent physically active and the amount of time they spent sedentary during those seven days. After these assessments, the team will keep track of them for one year. Of note, exercise training will not be offered as part of this proposed study. The number of deaths during that one year will be recorded, and the team will investigate any links between the times spent being physically active or sedentary during the day with survival.

Immunotherapy is an exciting treatment for mesothelioma. It works exceptionally well for some cancer patients, but there are side effects, and it is expensive. We want to be able to tell before treatment begins which patients will benefit and predict and prevent any bad reactions. Every person has a unique immune system and we can define features of that system like fingerprints. But these fingerprints change with time and wellness. Our study will map the changes associated with successful immunotherapy to see if we can predict therapy outcome.

The benefit of this study is that it will allow us to find out early in a treatment plan if that plan is working so that it can be altered if it is not.

T cells are specialised cells of the immune system that recognise and kill cancer cells. The team will examine how T cells become activated to kill cancer cells, which activation mechanisms correlate with improved survival, and explore new ways to ‘arm’ T cells for improved cancer killing ability. This will allow us to better predict which patients will benefit most from treatment and identify new ways of boosting the cancer killing ability of T cells for more effective treatment of mesothelioma, melanoma and solid cancers.

Our early data suggests for successful treatment patients require a balance of both ‘hot’ and ‘cold’ signals to drive a finely tuned ‘warm’ environment. An ‘overheated’ response drives a short but ultimately ineffectual immune response, which may explain why some patients with a ‘hot’ tumour fail to respond to therapy. Using current technology, we can investigate the mechanisms driving ‘warm’ responses to recapitulate them in the laboratory. Using this knowledge, we can stratify patients and deliver personalised therapies to switch them from ‘overheated’ or ‘cold’ tumours to ‘warm’ tumours to improve their response to current therapies.

This project will explore what psychosocial support patients with advanced cancer use, how it impacts them, and the costs and benefits of using psychosocial supportive care. This will be achieved by looking at what research has been done in this area, interviewing patients with advanced cancer to learn about their experiences, and undertaking a cohort study, where patients will be surveyed over six months to look at their needs, distress, and support services use over time.

Understanding the needs and service use of patients with advanced cancer will help to make sure the best support is being provided to lessen the distress and suffering they may experience.

Immunotherapy is an exciting treatment for mesothelioma, working to boost a patient’s immune cells (in particular T cells) to clear tumours. Clinical trials combining chemotherapy and immunotherapy can be an effective treatment in some cancer patients, whilst other patients gain no benefit. This may be due to each patient having different T cell receptors (TCRs) or keys that need to unlock the immune system to produce a successful anti-tumour immune response.

With the current technology to study millions of keys at the same time, this project will map distinct combinations of keys associated with a successful anti-tumour immune response, to see if we can predict chemo-immunotherapy outcomes.

The project will determine if muscle structure:

1) changes during treatment,

2) is associated with treatment tolerance,

3) differs between treatment groups, and

4) can improve with resistance exercise.

Muscle structure will be measured using pre- and post-treatment CT scans. Treatment tolerance information will be collected from medical records. A group of women will participate in an exercise program to assess if exercise can improve muscle structure and function.

This research will investigate:

1) the usefulness of muscle structure to identify women with poor treatment tolerance and survival,

2) the potential of exercise to improve muscle structure and function.

Results will inform the development of better supportive care for women with advanced OC.

This project has two parts:

1. To get a better understanding as to why some GIST re-grow after surgery and whether it would be possible to predict the outcome by looking more closely than before at the cancer’s make-up. New technologies will be used and a multi-disciplinary collaboration between clinicians, biologists and bioinformaticians to look at every single cell the cancer harbours to get a better understanding of the cancer “support cells” and how they may foster cancer re-growth.
2. It is known that GIST that grow have escaped detection by our immune system. Immune cells usually patrol our body and fight infections and are also supposed to destroy cancers. Whilst some immune cells are found in GIST, it is not clear how to attract more of these cells into the cancer core and program them to fight the cancer from “inside”. The team has already developed new drugs which work in pre-clinical models of pancreatic cancers and improve therapy. These drugs will be applied to pre-clinical GIST models with the hope to improve Gleevec therapy for longer lasting anti-cancer results.

Therefore, this research program aims at improving GIST prognostics and developing new therapies which harness the immune system.

The team recently showed a clinic-based targeted and supervised exercise and nutrition program to be effective in reducing fat mass by ~3kg in these men. The problem is that not all men would have access to such a program, such as those in regional, rural and remote settings, or have the financial ability to pay. Telehealth has emerged as a viable way to deliver healthcare. The aim of the project is to determine if the program delivered via telehealth is as effective as the supervised clinic-based program for fat weight loss, reducing cardiovascular disease risk, and enhancing physical and mental health in overweight/obese men with prostate cancer.

The study will recruit 104 overweight/obese men with prostate cancer and current or past usage of hormones and randomise them to a telehealth delivered program or the supervised clinic-based program for six months and then follow them for an additional six months. The clinic-based exercise program, which comprises of resistance and aerobic training, with nutritional advice will be the same as that in the pilot study and will be adapted to be delivered by telehealth using the latest technologies such as video chat with remote monitoring.

If the telehealth delivered program is effective, then it can be rolled-out at a low cost to patients, regardless of their financial position or where they live.

The facility will be located on the QEII Medical Campus and is scheduled to open in early 2022. The WA NIF Node will soon offer a full-service suite of research dedicated human imaging equipment and expertise. The new equipment includes a 3T MRI, a digital PET/CT and the accompanying GMP lab for the production of PET radiotracers. Support staff and experts will run support programs to access the imaging equipment. The project is strongly collaborative with 14 organisations committing funding and is multidisciplinary, bringing together the skills of clinical researchers, technical staff, imaging specialists and informatics experts. The new facility is a statewide initiative, which addresses the current lack of dedicated imaging research infrastructure in WA. The expanded facilities will be open to all local research institutions.

This fully integrated facility will allow researchers to lead and collaborate in a diversity of clinical trials. Access to imaging facilities for human research will have benefits for the personal health and wellbeing of all West Australians. The WA NIF node facilities will be highly enabling for translational research and have broad applicability across all medical fields particularly oncology, respiratory conditions and neurology. As a Node of the Australia-wide National Imaging Facility (NIF), the WA Node will collaborate with the other nodes and adhere to the federal strategy for innovative research.