Grantee: Dr Yu Heng Lau 

Administering Institution: University of Sydney

Amount: $675,000

Project: Developing targeted therapies for gliomas by peptide-assisted fragment optimisation

I aim to develop a first-in-class targeted therapy to target gliomas, the most common type of brain tumour. With current treatment options that involve a combination of non-targeted chemotherapy, radiotherapy, and surgery, this severe disease has one of the lowest 5-year survival rates of all cancers (22%), with minimal improvement seen over the last 30 years. There is an urgent need to improve patient outcomes through the development of new 'targeted therapies’, which promise greater efficacy and less side effects in the treatment of gliomas.

In the search for new targeted therapies, traditional chemical techniques used in the drug discovery process have generally failed against the therapeutic targets found in gliomas. My research will investigate whether a new drug discovery technology I have developed - Peptide-assisted Fragment Optimisation (PaFO) - can lead to the successful discovery of new and more effective targeted drug candidates for treating glioma.

PaFO uses the power of cutting-edge 'peptide display' technologies (Chemistry Nobel Prize 2018) to rapidly test trillions of variants of potential drug molecules all at once. The exceptional throughput and speed of PaFO will accelerate the identification of potent glioma drug candidates.

In my project, I will use PaFO to generate potent drug candidates that are validated in vitro against novel glioma targets, ready for downstream pre-clinical studies in cell-based and animal models of glioma, through collaborative support of Children's Medical Research Institute and industry partner Tessellate Bio.

Grantee: Dr Thanh Nho 

Administering Institution: University of New South Wales

Amount: $668,081

Project: Extending the Reach of Soft Micro-endoscopic Robot for Early Detection and Treatment of Epithelial Carcinomas

Epithelial Carcinomas (EC) are the most common cancers, occupying ~80% of all cancers worldwide. Initially, EC grows from epithelial layers of tubular structures in breast, lung, prostate, pancreas, and other organs. Early EC is silent. Overtime, it progresses to invasive cancer and spreads to surrounding organs, becoming fatal. Many EC cases are diagnosed late, making early detection and treatment crucial for increasing survival rates. Although medical imaging (CT/MRI/Ultrasound/X-ray) is the primary method for EC screening, they are unable to detect small tumours (e.g., <2 mm in breast, <3 mm in lung, <8 mm in pancreas), resulting in many missed cases (e.g., ~10%-35% for breast, ~62% for pancreas).

To confirm the presence of EC, cytological techniques which collect cell clusters/fluids and biopsies which extract tissue samples from suspected regions are employed. However, biopsies cannot be performed if a lesion cannot be imaged while cytological techniques are unable to precisely locate the cancer site. Furthermore, current imaging methods are associated with many false positives (e.g., ~21.3% for breast, ~13% for lung). This inaccuracy leads to unnecessary surgery, complications, and extra costs.

To address these challenges, this fellowship develops the first micro-endoscopic soft robot capable of accessing hard-to-reach tubular structures and detecting abnormalities via a mini-camera. The EC presence will be re-confirmed via onboard bioelectronics, which can also be used for in-situ tumour removal. This technology will add a new clinical tool into existing EC screening and treatment program in NSW, Australia, and worldwide, significantly enhancing EC patient’s outcomes and lowering healthcare cost

Grantee: A/Prof Daniel Steffens

Administering Institution: University of Sydney 

Amount: $675,000

Project: Supportive Multimodal Approach to Accelerate Recovery Following Cancer Surgery

Bowel cancer, also known as colorectal cancer, is one of the most common cancers in Australia, with about 15,000 new cases diagnosed each year. While surgery is often the main treatment, it can lead to complications and slow recovery, with some patients taking up to a year to return to normal function. This not only affects patients' quality of life but also results in extended hospital stays and high healthcare costs.

This fellowship aims to improve outcomes for bowel cancer patients undergoing surgery through three innovative approaches:

(i) Developing an online tool to identify high-risk patients before surgery, allowing for targeted interventions.
ii) Testing a virtual multimodal intervention that provides specialised support before and after surgery.
(iii) Co-design and test an AI-powered, Avatar-based video messaging system to support patients throughout their bowel cancer treatment journey.

These approaches aim to better prepare patients for surgery, reduce complications, speed up recovery, and lower healthcare costs. The research will also ensure that support is accessible to all patients, including those in rural/remote areas or from diverse backgrounds.

By combining technology with personalised care, this project seeks to transform bowel cancer treatment in NSW. The goal is to improve patients' survival rates and quality of life while making the healthcare system more efficient and cost-effective. This research aligns with NSW's cancer care priorities and could set new standards for bowel cancer treatment across Australia and beyond.

Grantee: Dr Fei Deng

Administering Institution: University of New South Wales

Amount: $597,900

Project: Autocatalytic CRISPR biosensor for ultrasensitive ctDNA detection towards precision oncology

Cancer patients require personalised treatment. Blood-based genetic testing of circulating tumour DNA (ctDNA) provides molecularly precise, real-time, and actionable information to guide care of cancer patients ahead of clinical or radiographic indicators. However, a research gap exists in conventional amplification techniques (e.g. PCR), which require highly specialised laboratories and equipment, and unable to avoid amplicon contamination.

This project aims to create innovative, cost-effective DNA biosensors for noninvasive cancer monitoring through detecting circulating tumor DNA (ctDNA) in blood. These sensors, designed to target specific cancer mutations, will provide rapid results (<15 minutes), cost less than $1 per test, and offer laboratory-level accuracy. It will enhance cancer monitoring, detecting therapy resistance and disease recurrence, and could potentially replace traditional biopsies, making cancer care more accessible and efficient.

Grantee:Dr Nicola Meagher

Administering Institution: University of Sydney

Amount: $500,740

Project: Aspirin use and the tumour immune microenvironment for improved ovarian cancer outcomes

There is growing interest in understanding whether common medications can add benefit to standard cancer treatments. We have evidence that aspirin/non-steroidal anti-inflammatory medications are linked to improved outcomes for ovarian cancer patients. One possible explanation is an influence of these medications on immune response to the tumour. We know that the presence of certain immune cells within a tumour is associated with a better chemotherapy response, and a better patient outcome. I will perform analyses of large-scale international datasets that include medication use, robust biological information about tumour immune cells, clinical features of the cancer and patient outcomes.

The overall goal is to understand how aspirin use is linked with longer ovarian cancer survival. A successful outcome will provide evidence to develop a prospective clinical trial to directly test whether aspirin contributes to a better immune response in ovarian cancer and results in improved patient outcomes.

Grantee: Dr Nicholas Hindley

Administering Institution: University of Sydney

Amount: $518,767

Project: Maximising access while minimising toxicity with adaptive lung cancer radiation therapy

Lung cancer is the leading cause of cancer-related death and the fifth most commonly diagnosed cancer in Australia. Patients with locally advanced and metastatic disease face particularly poor prognoses with 5-year survival rates of 17% and 3% but cannot access the most effective treatments.

77% of lung cancer patients will benefit from radiation therapy and hypofractionated treatments, where high doses are delivered in concentrated treatment sessions, have been shown to improve overall survival with 10 times fewer hospital visits. However, 1 in 2 lung cancer patients are ineligible for these highly effective treatments, because they suffer from metastases and we currently cannot adapt hypofractionated treatments to multiple independently-moving targets as patients breathe.

To maximise access to the most effective treatments while minimising radiation-induced toxicities, I invented Voxelmap, a patent-pending artificial intelligence system that tracks tumours and organs during lung cancer radiation therapy. The current standard-of-care irradiates static target volumes that incur unnecessary healthy tissue damage. Voxelmap shifts the paradigm from these large, static targets toward smaller volumes that are dynamically shifted during treatment.

Through this fellowship, I will demonstrate the first use of tumour and organ tracking on a clinical radiation therapy system. This will be achieved by (i) developing a learning framework so Voxelmap adapts as patient physiology varies between treatment sessions and (ii) extensively testing the accuracy of Voxelmap on a clinical system at Royal North Shore Hospital.

Grantee: Dr Rebecca Simpson

Administering Institution: University of Sydney

Amount: $596,259

Project: Targeting microbiome-immune crosstalk to improve immune checkpoint inhibitor immunotherapy outcomes

The microbes in our gut (microbiome) influence immune processes throughout the body. This includes how patients respond to immunotherapies. These therapies aim to reactivate a patient’s own immune system to recognise and kill tumour cells. However, nearly 50% of patients with advanced melanoma who are treated with immunotherapies still die of their disease. Furthermore, immunotherapies can cause severe side effects, that can be life-altering and result in patients having to stop treatment.

Accumulating evidence over recent years, including our own research, has established the importance of the pre-treatment gut microbiome for subsequent immunotherapy outcomes in terms of both tumour clearance and the development of immune-mediated toxicities. As such the gut microbiome is of great interest both as a potential biomarker (indicator) to predict clinical outcomes as well as a therapeutic target to improve the effectiveness and safety of treatment. However, without a detailed understanding of how the gut microbiome influences immunity throughout the body, and which microbial components are responsible we cannot design targeted, evidence-based interventions to augment therapeutic outcomes for patients.

By leveraging access to important samples from a unique clinical trial cohort and complimentary pre-clinical mouse models utilising diet to modify the gut microbiome, this research program seeks to increase our understanding of how gut microbes interact with the immune system to shape patient responses and clinical outcomes. This research will facilitate the development of biomarker and intervention approaches that will improve treatment outcomes for cancer patients.

Grantee: Dr Emma Charters

Administering Institution: University of Sydney

Amount: $525,000

Project: Restoring Function Following Jaw Reconstruction in Patients with Oral Cancer

Mouth cancer treatment involves removing and reconstructing part of the jaw followed by radiotherapy. To eat, talk and care for their teeth patients need their bone to heal and their mouth to open. Difficulty opening the mouth is called trismus, it is a major problem after mouth cancer treatment, significantly restricting function and quality of life.

RestorabiteTM is a new mouth stretching device that is designed to prevent and treat trismus. The low cost of RestorabiteTM means anyone can use it, not just those from high income earning backgrounds. It is safe, because it has different levels of difficulty, allowing people to exercise at the level that is best suited for them.

We have shown that Restorabite works, but what is still unknown is how to optimise and personalise its use to help not just mouth opening but also bone healing after mouth surgery. We will work with the engineering department at the University of Sydney who will use mathematical modeling software and the patient’s medical scans to target the exercises more precisely.

This has not been done anywhere else in the world. It will not only help many vulnerable people who require life changing cancer treatment, but will also make Australia the international leader in improving the function and quality of life of the growing number of people affected by this type of cancer. In doing so, more people will receive good nutrition, be less anxious, speak clearly, get good teeth care and maintain their work and social roles.

Grantee: Dr David Chan

Administering Institution: University of Sydney 

Amount: $592,737

Project: Unravelling the complexity of serial PET imaging in neuroendocrine neoplasms

In 2023, over 5,500 Australians were told they have neuroendocrine neoplasia (NEN), and more than 25,000 are currently living with NEN. NENs are a major clinical challenge as they arise from multiple sites throughout the body and vary significantly in their behaviour. Some patients can have stable disease for over ten years (low-grade NEN), while others with more aggressive disease may only survive for one year following diagnosis (high-grade NEN). Choosing optimal NEN treatment and predicting survival outcomes for each patient relies on accurately determining NEN grade.

Dual PET imaging using a combination of the agents 68Ga-DOTA-octreotate (DOTATATE) and 18F-FDG (FDG), called dual PET, is increasingly used to assess tumour biology. This whole-body modality avoids the risk of biopsies, is cost-effective, and can be replicated accurately and evaluated objectively.

However, despite the increased use of dual PET, there is no data to guide the interpretation of changes in PET imaging observed throughout treatment (serial PET). This poses a significant challenge for clinicians and patients and causes confusion and anxiety as optimal outcomes rely on an accurate understanding of disease biology and finding the right time to change therapies. As it currently stands, patients undergo serial PET without clarity on what the results mean.

This project will use new technology to extract and interpret vast amounts of information generated by serial PET imaging. Understanding these changes will allow clinicians to translate this promising imaging technology into the clinic to ensure optimal outcomes for NEN patients.

Grantee: Dr Chandrima Sengupta

Administering Institution: University of Sydney 

Amount: $515,716

Project: The next generation of tumour targeting technology: Halving toxicity and treatment time with real-time adaptive liver cancer radiation therapy

This academic-clinical-industry-consumer partnership project will develop and clinically translate a liver cancer targeting technology leveraging our team’s world-leading expertise in targeted radiotherapy. Real-time cancer targeting has been shown to halve treatment-related toxicity in a randomised clinical trial for prostate radiotherapy, when tumour motion was imaged and corrected for using $10M+ specialised devices. Extrapolating this outcome to liver radiotherapy, real-time cancer targeting becomes a stringent requirement, as liver tumours exhibit motion of several centimetres, and are near healthy radiosensitive liver tissues, bowel and stomach.

The unmet clinical need is that 89% centres in NSW want real-time cancer targeting for liver radiotherapy but are unable to access $10M+ specialised devices. I will pioneer a world-first liver cancer targeting technology using real-time x-ray images to image and correct for the liver tumour and nearby organ-at-risk (OAR) motion. I will then convert this method into clinical software and experimentally evaluate the performance of the technology. I will then halve the treatment time by enabling real-time motion adaptation with couch tracking that keeps the radiation beam aligned with the tumour throughout treatment. The technology will enable submm cancer targeting accuracy on standard radiotherapy devices, available to all patients in NSW.

I will leverage my ongoing collaboration with experts in radiation oncology, consumers and industry partners ensuring the proposed research positively impacts treatment outcomes. Successful completion of this project will lead to its prospective use in an approved clinical trial and adaptation of the technology to other radiotherapy centres, benefitting thousands of cancer patients in NSW.

Grantee: Dr Michaela Hall

Administering Institution: University of Sydney 

Amount: $592,932

Project: Equity and optimization of cervical cancer prevention in women living with HIV: advancing methods, impact and accessibility

We will determine optimal combinations of cervical screening and HPV vaccination programs for women living with HIV in low and lower-middle income countries. This will be achieved by using a detailed mathematical model of HIV and cervical cancer to simulate a large range of hypothetical scenarios of cervical screening, HPV vaccination and HIV control and comparing predicted cancer outcomes for each. The outcomes from this modelling will be hosted on the "Elimination Planning Tool", a free online resource where users can select their desired combination of cancer interventions and see the expected outcome of implementing them.

While the modelling is being developed, we will work closely with our collaborators in Tanzania, through our World Health Organisation partnerships, and in Papua New Guinea, through the EPICC (the Elimination Partnership in the Indo-Pacific for Cervical Cancer) Australian government regional aid grant, to ensure our work is of maximum value to the communities it aims to benefit. By enabling policymakers in all countries access to high quality evidence on the impact of cancer control in women living with HIV, they will be enabled to better serve their communities and prevent cervical cancer in all women, including those living with HIV.

Grantee: Dr Carolyn Mazariego

Administering Institution: University of New South Wales 

Amount: $600,000

Project: Scalable & sustainable implementation of tumour-specific patient reported outcome collection programs to ensure person-centred cancer clinical care

Every day in New South Wales, around 130 people are diagnosed with cancer. While new medical treatments have increased survival rates for many types of cancer, including prostate, breast, and colorectal cancers, improving the quality of life for these patients remains a challenge. Most cancer patients only spend about 10-15 minutes with their doctors during follow-up appointments, amounting to less than 1% of their time over a five-year treatment journey. This limited time with healthcare providers makes it difficult to address the many physical, mental, emotional, financial, and social issues patients face.

To tackle this problem, my program of research will develop specialised Patient Reported Modules (PRMs) for prostate, breast, and colorectal cancer patients. PRMs are survey tools that allow patients to report their wellbeing and concerns, which can then be addressed by their healthcare team. By tailoring these PRMs to specific types of cancer, we can ensure that all aspects of a patient's well-being are considered in their care plan.

These tumour-specific PRM will be tested in three diverse regions: the Mid-North Coast, South Eastern Sydney, and South Western Sydney. This approach will help identify gaps in current cancer care, design effective PRMs with input from patients and healthcare professionals and evaluate the impact on patient care and outcomes.

My goal is to improve the quality of life for cancer patients by making sure their voices are heard and their needs are met, ultimately setting a new standard for personalised cancer care in NSW.

Grantee: Dr Guocheng Fang

Administering Institution: University of Technology Sydney 

Amount: $598,593

Project: Engineering human intestinal microphysiological system for studying colorectal cancer resistance and screening pre-clinical therapeutics

Colorectal cancer is a leading cause of death in Australia, affecting people of all ages and genders. One major challenge in treating this cancer is its resistance to current therapies, primarily due to the complexity of cancer microenvironment. The most direct and effective approach relies on batch screening of drug combinations using laboratory models. However, animal models often fail to predict human responses accurately due to species differences. Organoid models, such as colorectal cancer organoids, show great promise but lack critical physiological features of the human gut, including rhythmic peristalsis and blood vessels. This gap raises concerns about their accuracy in studying drug resistance and testing treatments.

This proposed research aims to engineering the human intestinal microphysiological system to advance colorectal cancer organoids. My expertise in microfluidic techniques and tissue engineering will create a more realistic intestinal environment for these models, incorporating peristalsis, vascular networks, and the complex cancer microenvironment with supportive cells and structures.

With such models, I will investigate why cancers resist treatment at both pharmaceutical molecule level and gene level, and test various drug combinations to identify more effective therapies. By understanding the roles of mechanics, blood vessels, and surrounding environment in drug resistance, I can develop better preclinical treatments for colorectal cancer.

Ultimately, my goal is to create a more reliable model for studying colorectal cancer. This new model could also be adapted to research other types of cancer, such as stomach, lung, and breast cancers, potentially leading to broader advances in cancer research and treatment.

Grantee: Dr Shona Ritchie

Administering Institution: University of New South Wales 

Amount: $497,584

Project: Repurposing PCSK9 inhibitor evolocumab to enhance the efficacy of chemotherapies in pancreatic cancer

Pancreatic cancer (PC) has one of the worst outcomes of all cancers. High incidences of metastases and frequent therapy resistance are key drivers of these poor outcomes. There is therefore an urgent need for innovative treatment options for PC.

During establishment, PC tumours become hypoxic and nutrient-depleted. Cancer cells undergo significant metabolic rewiring to survive these harsh conditions. Through an unbiased multi-omics analysis, I recently discovered that a cholesterol regulating protein, PCSK9, is significantly overexpressed by highly-metastatic PC Cells.

Due to the important role in cholesterol uptake, several PCSK9 inhibitors are used in-clinic for the treatment of high cholesterol, including evolocumab (Repatha®). Strikingly, I found that high expression of PCSK9 is significantly associated with poor outcomes in PC patients. Furthermore, I found that evolocumab can significantly improve chemotherapy efficacy in short-term models, revealing PCSK9 as a novel target for this deadly disease.

I now aim to explore how and when evolocumab co-treatment can improve chemotherapy efficacy in PC. I will use state-of-the-art in vivo imaging to optimise this new treatment regimen, in real-time. This will be coupled with comprehensive assessment of PCSK9 in patient specimens, and will utilise patient-derived xenografts (PDXs), allowing for a rapid stratification within clinically-relevant models.

Overall, the goal of this Fellowship is to utilise advanced in vivo imaging techniques to investigate PC response to evolocumab +/- gem/Ab at both single-cell and systemic levels. By integrating precision oncology methods, I aim to identify PC patients that could benefit from repurposing evolocumab, to enhance the efficacy of chemotherapy.