2024 successful cancer researchers and projects

Current immunotherapy drugs are antibodies, which are expensive to manufacture. These antibodies need to be administered by intravenous injections, which are invasive for patients and financially burden the health system, as they need to be administered by a health professional.

We aim to develop an oral drug that boosts the immune response against cancer, improving outcomes for cancer patients in Western Australia and globally. Our team has identified a specific drug target (a protein) in immune cells that impedes the body’s immune response against cancer cells. Inhibiting this protein improves the outcomes of immunotherapy treatment in laboratory models. We have discovered drug-like inhibitors of this protein and aim to demonstrate proof of concept and develop these further towards clinically useful drugs that are optimally effective with minimised side effects.

To provide hope to cancer patients, our project will develop a safer and more effective way to treat patients who are having surgery to remove their cancer, which stops the cancer from ever coming back. To do this we have made a special gel, which can be loaded with anti-cancer drugs, and applied in the wound when the surgeon is removing a tumour. The gel is naturally broken down by the body over time, which causes the drug to be slowly released. This means patients can go home sooner and get on with their lives while still receiving their treatment.

In this project we are developing a new class of drugs, using the same technology as the COVID-19 mRNA vaccine. These drugs are messengers that instruct the body to make signals which activate the immune system to attack cancer cells. While vaccines can be injected in your arm, it can be more difficult and less effective to inject something into a patient’s tumour. We believe that our gel-based surgical application will be the perfect way to delivery this new kind of drug. Now we need to find the right messengers to turn on the immune system and optimise the gels to deliver them, so we can stop sarcoma coming back after surgery.

Our research reveals that metals like copper accumulate in mesothelioma, fuelling tumour growth and aiding in evading the immune system. By using drugs that bind to copper, we aim to reduce its availability to cancer cells, consequently boosting the immune response against the cancer.

To succeed, we need to test these copper-binding drugs in combination with current treatments to investigate how copper helps cancers evade the immune system. We will employ cutting edge techniques to analyse the amount and location of copper, how copper impacts genes and proteins within tumours.

These copper-binding drugs are already approved for use in other diseases, are low in toxicity, and are cost-effective. This means they could swiftly become a part of treatment options for patients. While this work is aimed at improving treatments for mesothelioma, copper binding drugs could be used to treat many different cancer types because copper accumulation is common in many cancers.

We propose to develop novel biomarkers in blood by measuring a group of signals, called epigenetic histone modifications; these signals bridge environmental risks with gene expression in the tumour cells and could be used to detect environmental risk factors contributing to breast cancer development or progression. These signals could be used for risk prediction and early detection of breast cancer.

We will measure these signals using genomic sequencing technology and advanced computational technology, machine learning. Using these signals, we could predict women who are under the risk of developing breast cancer and detect breast cancer in women as early as possible. The outcomes of our study will support the reduction of breast cancer incidence, increase survival rates, and reduce treatment burden for both patients and the healthcare system. In the long run, such novel biomarkers in combination with sufficient approaches for preventing breast cancer would be the ultimate path to end breast cancer.

Previously, we found drugs that improve how chemotherapy kills cancer cells (called inhibitors of the DNA damage response) and showed they are effective for MB treatment. One such drug, prexasertib, worked so well with chemotherapy that we opened a phase-one MB clinical trial in Australia and USA.

THIS PROJECT builds on our new evidence that these drugs also improve the effectiveness of radiation-therapy while simultaneously stimulating the immune system. To test the treatments as accurately as possible, we developed world-first, “child-like” MB mouse models that have growing brains and developing immune systems. This is instead of using adult mice with fully grown bodies, as are typically used worldwide. We show that these “child-like” mice exhibit important differences in the way the cancers grow and immune systems function. This suggests our results will better reflect the “real-world” and have a better chance of working in the clinic.

Our objective is to develop innovative targeted therapies for TNBCs and HER2+ patients. We have discovered a novel protein, called Rab12 which acts as a “protector”, suppressing cancer growth and inhibiting therapy resistance. Unfortunately Rab12 expression is shut-down in these cancers. This proposal seeks to develop state-of-the-art delivery methods to transport Rab12 inside cancer cells, where it can reclaim its “protector” role.

In Aim 1 – we will measure Rab12 in a large collection of BCs tissues with known clinical outcomes. This will help characterise the subset of patients with low Rab12 expression that are most likely to benefit from our new treatment.

In Aim 2 – we will turn on Rab12 expression in TNBC and HER2+ BCs to find out if Rab12 can make other therapies, such as chemo- and anti-HER2 therapy more effective.

In Aim 3 – we will produce a synthetic derivative of Rab12 that can be targeted and delivered through the bloodstream. We will use state-of-the-art chemistry to deliver Rab12 into relevant BC mouse models and assess effects on tumour growth.

This work will produce novel therapeutics for recalcitrant BCs. Beyond BC, this treatment could benefit many other patients, including those with colon and liver cancer.

Prompt treatment with surgery, radiotherapy and chemotherapy gives patients the best outcome from lung cancer. Additionally, discovery of immunotherapy has had a profound impact on lung cancer treatment, prolonging survival with a small chance of cure. Also, our knowledge of gene malfunctions that cause cancer has been increasing, some of which can be targeted to treat the cancer. However, immune and targeted treatments can only be used where the cancer has been tested to see if these are suitable therapies.

No-one knows whether Aboriginal or remote patients experience delays with or miss out on conventional therapies. It is also not known whether all receive testing, have differing rates of immune sensitive or targetable cancers or whether those suitable for these treatments receive and complete them. We will be seeking this information  and looking at whether deficiencies in treatment explain the worse survivals for these groups. Where there are missing tests we will carry them out to complete the picture of lung cancer types in these patients. We will also do some new tests, not currently standard in lung cancer, to get a more detailed picture of the mutations that cause Indigenous cancers and the patients immune response to them.

Our expert team then has the experience and connections to plan and deliver better services to address the gaps found.

We have recently analysed tumour samples collected from children with high-risk neuroblastoma before and after chemotherapy. We found that the presence of immune cells before treatment was linked with a good response to chemotherapy, but also, that prolonged activation of the immune response after chemotherapy was associated with poor survival. This information could help us predict which children will respond to chemotherapy. Now we want to confirm these results in an independent group of patient samples collected by the Westmead Children’s Hospital and understand how immune cells and tumour cells communicate with each other to drive a good response to chemotherapy. Validating our results in a second group of patients is a necessary and important step in translating this work to the clinic.

This will help us define an “immune” fingerprint that predicts response to treatment, having immediate impact on clinical decisions, sparing kids, and families from 2 years’ worth of pointless toxic therapy and providing earlier access to clinical trials. In addition, we will identify new targets for immunotherapy that boost the cancer killing activity of immune cells, turning non-responding patients into responders thereby developing more effective treatment for high-risk neuroblastoma

Recent studies found that signalling molecules called cytokines suppress prostate cancer cell growth, which may have important implications for the survival of patients.  It has also been established that skeletal muscle is associated with survival of patients with prostate cancer and that muscle is the largest organ influencing cytokine levels.  Despite evidence of the role of skeletal muscle impacting the survival of patients through tumour-suppressive cytokines, translation of this biological knowledge into clinical practice is limited due to a lack of understanding of the differential impact of stage and treatment on muscle mass and cytokine levels. The research team are proposing to evaluate cytokines in the blood and body composition of 90 patients with prostate cancer (30 localised without treament, 30 localised with treatment, and 30 advanced with treatment) and 30 healthy subjects as well as looking at the impact of these cytokines on prostate cancer cell growth. Benefits of this research will include our first understanding of the impact of muscle mass on the anti-cancer cytokine levels across the stages and treatments of prostate cancer.  This will help explain a major biological reason for the survival advantages exhibited by physically active patients and inform more optimal exercise prescription tailored to the patient.

The impact of allergic reactions on patients’ cancer treatment (for example, on stopping or delaying treatment), cancer recurrence and survival, and patients’ physical and psychological health is unknown. Nor, in WA, is there a pathway or dedicated service to manage such reactions although they can occur with almost all cancer treatments. Here, we aim to understand the nature and impact of such drug reactions and explore the associated patient experience. We will also pilot a clinic service involving cancer and allergy specialists providing specific advice to patients and their treating cancer team on management of allergic reactions to anti-cancer drugs.

To do so, we will interview patients who experienced allergic reactions to anti-cancer drugs to explore the symptoms associated with their allergy and the impact of the reaction on their cancer care and wellbeing. We will then integrate a new service (Allergo-Oncology service) into the already established drug allergy clinic at Sir Charles Gairdner Hospital. Understanding the immune pathways underpinning allergy to anti-cancer drugs within a patient centred model of care is likely to prevent delays in cancer treatment, provide access to more treatment options and provide specific support options for cancer patients across WA.

Further, overweight and obesity are associated with decreased survival in this cancer group. These women need support in using the time before surgery to physically prepare for surgery. Being fitter before surgery will reduce the risk of surgical complications and accelerate recovery post-surgery. Interventions delivered before surgery to prepare patients for surgery and accelerate recovery have been shown to reduce post-surgical complications and length of hospital stay in several cancer groups.

These interventions also improved patients’ physical function (ability to perform basic activities of daily living) and quality of life. However, the effect of pre-surgical interventions has not been tested in endometrial cancer. I will investigate whether a six-week pre-surgical exercise and nutrition intervention is effective in decreasing body fat and improving physical function, thus improving surgical outcomes and quality of life in endometrial cancer patients. The exercise intervention will be done three times a week with weekly supervision and with support from an exercise physiologist.

Participants will receive nutrition education, a low-calorie diet, and weekly follow-up from a dietician. This study will provide important information to help endometrial cancer patients better tolerate the physical challenges of surgery and enhance their post-surgery recovery

The University of Western Australia

By combining these existing medicines with low-dose radiation therapy, I can determine if

1. this more effectively kills brain cancer than radiation alone (which is the standard treatment today) AND
2. If this reduces the side effects of radiation, since the dose is lower. If successful I will move this finding into clinical trials quickly, as this will be the first time a new treatment for brain cancer has been identified in more than 30 years.

~9 cancers go undetected per 10,000 women screened. Despite the success of BreastScreen programs in preventing breast cancer deaths, there is clear potential for improvement. This research program aims to reduce breast cancer mortality in Australia by improving early detection using three approaches: increasing screening participation, co- producing primary care pathways to improve screening, and facilitating consumer-driven research

Specifically, this research aims to:

1. Evaluate a novel intervention targeting obesity-related barriers to mammographic screening participation within the BreastScreen Western Australia (WA) program via the BreastScreenPlus Project.
2. Co-design and implement personalised screening pathways for women within primary care, as part of our NHMRC Centre for Research Excellence, MyBRISK, and as part of a Cancer Council WA Collaborative Cancer Grant.
3. Co-develop an interactive web-based platform that facilitates prioritization and co-production of consumer-driven research projects to improve screening outcomes in Australia This program of research will improve breast cancer screening and save women’s lives. In extensive consultation with stakeholders, our expert teams will deliver highly-translatable outputs that will reduce breast cancer mortality by improving early detection of the disease.

After developing a new analytical platform that involves acquisition of large amounts of biological information from thousands of liver cells with unprecedented level of detail, the aim is to identify molecular signatures that can predict liver cancer before it develops.

It is important to predict cancer as early as possible as liver health can be restored before the damage becomes permanent and catastrophic. Early detection will improve survival and quality of life, as seen with other cancer types for which screening programs are in place.

The purpose of this project is to investigate the effects of exercise on blood flow and oxygenation in tumours of men with prostate cancer undergoing radiotherapy.  I will first examine if a single exercise session can improve tumour blood flow and oxygenation.  In addition, I will examine long-term effects of exercise training over the course of radiotherapy on tumour blood flow and oxygenation as well as whether exercise can reduce treatment-related side effects such as bladder and bowel symptoms.

The impact of these results, if proven effective, are enormous.  Reducing urinary side effects addresses a major issue for prostate cancer patients.  Furthermore, by demonstrating the effects of exercise on tumour blood flow and oxygenation, I hope to highlight exercise as a low-cost therapy that can enhance the effectiveness of cancer treatment.

The University of Western Australia

Unfortunately, research shows referrals only happen for fewer than 13% of people. This low number is unacceptable.

My research aims to increase the number of people who are referred to appropriate exercise services during cancer treatment. There are three phases:

Phase 1: Explore

Explore how cancer doctors and nurses in an organisation refer patients to exercise and what makes referrals hard so we can learn what is and is not working and why.

Explore how people receiving cancer treatment are receiving information about exercise and what they think is and is not useful about that information.

Phase 2. Design

Design a new system to increase the number of people who receive an exercise referral from their cancer care team. The new system will be designed by an advisory group of managers, cancer doctors and nurses, administrative professionals, and people who have received treatment from the organisation.

Phase 3. Evaluate

Evaluate the new system to see if cancer doctors and nurses use it, if it helps people receiving treatment recognise the importance of doing different types of exercise during treatment, and if it helps people participate in exercise during treatment.

The work will be used to develop resources to help guide others to establish an exercise referral process within their cancer care organisations and will increase the number of patients who benefit from exercise during cancer treatment.

Radiotherapy is given to more than half of all cancer patients and can even cure some cancers.  We know that radiotherapy kills cancer cells and stops them multiplying.  However, radiotherapy can also boost immune responses to cancer.  Combining radiotherapy with immunotherapy could greatly improve treatment responses.

This research aims to find the best way to combine radiotherapy and immunotherapy.  We have already found a particular combination that can cure 100% of tumours under the skin in mice. With more information, we may be able to apply radio-immunotherapy to humans. This project studies how radiotherapy changes immune cells to help them destroy tumour cells. We will test how well radio-immunotherapy treats cancer that has spread and attempt to treat tumours surrounding the lung, mimicking where mesothelioma occurs in humans.

This project will use mesothelioma mouse models and a highly precise X-ray machine for irradiations with the goal of providing evidence needed to start clinical testing of radio-immunotherapy for mesothelioma patients. This research will ultimately result in better treatment options and survival for many cancers.

During a patient’s treatment, accurately inspecting these images becomes challenging and potentially misleading, for e.g., treatment effects (such as inflammation) may appear to look like tumour recurrence on an MRI, which can cuse a premature halting of treatment. To be confident, doctors often must implement a “wait and see” approach for conclusive evidence which, with an aggressive cancer like glioblastoma, can be detrimental to a patient’s outcome.

Doctors don’t use the digital data available within medical images, which are made up of hundreds to thousands of numbers. Advancements in computing has opened an additional avenue of research where we believe that artificial intelligence can process this data to inform on a glioblastoma patient’s predicted survival or tumour recurrence. This can act as an addtional set of tools for doctors so that they can confidently pivot patient treatment earlier and with more accuracy, which is expected to improve survival.

These approaches will be applied to positron emission tomography (PET) combined with a radioactive tracer with demonstrated beneficial properties in glioma imaging called O-(2[18F]-fluorethyl)-L-tyrosine (FET). In parallel, we will also investigte the use of an automated artificial intelligence pipeline applied to a relatively new MRI sequence using amide proton transfer (APT), which has also shown promising predictive power for patient survival.

This project will utilize a new approach by employing a specific tool called Epi-CRISPR to switch off the new gene to inhibit the growth of EWS cells. We will also develop a new carrier for Epi-CRISPR to facilitate its clinical application. To achieve these goals, several lab assays and animal models will be used. This project is expected to improve the life expectancy of EWS patients and to make a paradigm shift in the scope of Epi-CRISPR applications in clinical trials that are not exclusive to EWS but extend to other types of cancer.

PC cells can communicate with other cells, like immune cells, by sending small bubble-like particles called exosomes. Exosomes are naturally released and carry many different molecules (proteins, lipids, genetic information and other substances) usually found inside cells. When other cells take up exosomes, these molecules are delivered and can change how the cell functions. Our research group recently discovered an important lipid molecule inside exosomes produced only by PC cells. This lipid is known to control normal immune responses but is also involved in various immune disorders, including cancer. In this project, we explore how exosomes transport this lipid to immune cells to stop their tumour-killing functions. We aim to see if blocking this transport can boost immune cells to find and kill cancer cells. We also want to study other materials inside exosomes from PC patients to know if they can be used as a non-invasive way to detect PC. This study will help us understand how PC cells control immune cells and may provide new ways to detect and treat this deadly disease.

While therapies that increase anti-cancer immune responses have shown promise, most patients do not benefit from immunotherapy.  New treatments are needed to help improve current therapies so they are more effective for all patients.

We have found that metals such as copper accumulate in mesothelioma, and are a major force driving tumour growth and helping the cancers to evade immune responses. Using copper-binding drugs, we aim to reduce the copper available to the cancer, and understand how it improves the anti-cancer immune cells needed to improve treatments.

To succeed, we need to test these copper-binding drugs in combination with current treatments to investigate how copper helps cancers evade the immune system. We plan to use microscopy to look closely at the different immune cells that are found in mesothelioma tumours, and see if altering copper changes the number of these cells.

These copper-binding drugs are approved for use in other diseases, are found to have low toxicity, are cheap, and have the potential to be rapidly adopted for patients.

Understanding how these drugs work to help the immune system may also help other cancer types in the future.

Researchers worldwide are studying the genes that cause ovarian cancer; however, the knowledge is incomplete. Identifying a gene(s) that has diagnostic and therapeutic value would immensely help improve ovarian cancer patients’ outcomes.

From studying ovarian cancer patient samples, Dr Woo’s research team identified the abnormal presence of a gene named ZNF148 that might drive ovarian cancer formation and aggressive growth. Dr Woo previously found a role for ZNF148 in aggressive breast cancers, however in ovarian cancer, nothing is known about the ZNF148 gene. This project aims to help build a foundation for studying the ZNF148 gene by establishing ovarian cancer cell lines that can be grown in the laboratory. These new cell lines will mimic the abnormal ZNF148 gene activity observed in ovarian cancer patients. This research will measure changes in the rate of cancer cell growth and their spread with respect to the ZNF148 gene activity.

Successful completion of this project will help identify ZNF148 as a new gene that causes the aggressive progression of ovarian cancer and will encourage the development of future therapeutic and diagnostic tools for improving the outcomes of ovarian cancer patients.

Serial bone marrow examinations are currently used to monitor patients but is an invasive and confronting procedure. We aim to reduce this burden for patients and the healthcare system by using a new blood-based test that we have developed. With this test, we can detect specific changes in the blood of patients diagnosed with myelofibrosis. My aim is to observe if these changes are reversed after a bone marrow transplant.

To do this, I will analyse samples before and after a bone marrow transplant from patients who are enrolled in clinical trials with our collaborators in the USA. The samples have already been collected and shipped to Perth. I anticipate that if the cancer-associated changes return to normal, then the patient has been cured. In contrast, if the abnormalities remain then this indicates that the cancer has persisted and more treatments will be needed. My project will provide an indication that our blood test has the potential to be used as a much less invasive monitoring tool to ease patient burden and improve their care.

Sarcomas are considered solid tumours, meaning they can be removed by surgery as a main treatment.

Our research aims to make a treatment that stops the cancer from coming back after surgery by applying a gel that contains molecules to help your body fight any remaining cancer cells in the area. These molecules are a type of messenger that your body already produces called mRNA.

The mRNA, which can also be found naturally in your body, are needed to make signals that tell your immune system to clean up any cancer cells after the surgery. Our treatment may help strengthen the natural body response by increasing the message to your cells to fight back against the cancer, helping to prevent it from coming back.

The antigen recognising T cells often become “exhausted” as the disease progresses and this is detrimental to patient health and treatment outcomes. This project aims to investigate what the antigens recognised by “stem-like” T cells are, and to determine if by vaccinating patients, we can return “exhausted” T cells to this beneficial, active “stem-like” state. This will be conducted in two steps, first by using a series of molecular techniques to identify the specific antigen recognised by “stem-like” T cells, and then by using an animal model to examine the effect of vaccination on “exhausted” T cells. If this research is successful, the project would look to use any newly identified antigens in current clinical trials, and to also implement vaccination in patient cases where “exhausted” T cells are thought to be a cause of worsening individual heath.

This information will be used to study four priority areas: What cell types are present in each tumour? ; Which drugs might kill these cancer cells, what fraction of cancer cells are likely to be resistant and why are some cancers resistant?; What changes between the cancer cells in a primary site when they move to a metastatic site?; and can new biomarkers be identified for early cancer detection and can cancer cells be detected in the blood?

Professor Elin Gray

Edith Cowan University

The Western Australia Melanoma Initiative (WAMI) is a research collaborative comprising basic and clinical researchers from WA, as well as their national and international collaborators. The clinical needs of our consumer representatives with lived experience of melanoma drives WAMI research agenda and the focus of this grant application. Our project aims to improve the outcomes of patients not benefiting from current therapies. WAMI will build upon current areas of excellence in melanoma research in WA, focusing on consolidating existing biobanks and developing an analytical pipeline to provide detailed molecular profiling for translational clinical studies.

WAMI’s overarching themes are: (i) implement adoptive cell therapy with tumour infiltrating lymphocytes (TILs) in WA and (ii) use advanced animal models, fundamental research and gene therapeutics to improve TIL and other cell therapies. Notably, TIL therapy is an effective form of cellular immunotherapy currently unavailable in Australia. The establishment of clinical experience in cell therapy for melanoma, and our innovative platform for improving and delivering additional cell therapies, will improve the lives of patients and enable translation also for patients with other solid tumours.

A special focus of WAMI is to identify which patient is most likely to require TIL therapy. By biobanking tumours and blood before and after immune checkpoint inhibitor therapy and TIL therapy, biomarkers that can help with patient stratification will be made clinically useful.

By creating a dedicated centre where RNA innovators work hand in hand with oncologists, consumers and patient advocates to design, synthesise, test and improve pilot RNA products, we will improve cancer outcomes in WA and give local cancer researchers a powerful competitive edge. We also have a niche, being the only proposed centre focusing solely on applying RNA technology for oncology treatments, giving a razor focus on cancer relative to other RNA hubs.

Our multidisciplinary approach brings together diverse researchers from oncologists to cell biologists, chemists and computer scientists. The ACRTC will support multiple WA research groups directly, with potential for new groups to benefit once established. Pilot projects incentivise collaboration as no single group has all the skills needed to produce a new drug – we must work together! In five years, we aim to be well progressed on a translational pipeline for 5 new treatments, as well as discovering innovative approaches and frameworks that can be used by other researchers for solutions for other cancer subtypes. Ultimately our goal is to get new therapies to the clinic to improve outcomes and quality of life for those afflicted by cancer.

New treatments are urgently needed to overcome drug resistance. One of the most exciting clinical development in recent years is the advent of immunotherapy. Immunotherapy harnesses the body’s own immune system to fight cancer. This treatment is already used for some advanced cancers such as melanoma, often with dramatic results. However, so far GIST has not been considered for immunotherapy. New research published in 2020 indicates that some GIST patients (approximately 50%) spontaneously display lymph node like structures which promote immune cell trafficking and indicate better overall survival.

This research proposal will build on these findings using our expertise in the field and incorporate a unique animal model to test how these lymph nodes can be induced to optimize immunotherapy. For this aim human cancers will be grown in a mouse which harbours a human immune system; this is currently the best model system for studying immunotherapy effects.

We will also collect clinical GIST cancer specimen and examine the numbers and characteristics of spontaneous lymph nodes by developing a new detection system. We expect that this will be useful to identify those GIST patients who will benefit from immunotherapy.

Overall, the goal of the project is to provide GIST cancer patients with new immune based treatment options by combining already available drugs, to overcome resistance and prolong survival.