|Nationwide conference support
A feasibility study towards the development of a microbiome-based screening assay for endometrial cancer
Over 600 women are diagnosed with endometrial cancer each year in New Zealand. Also known as cancer of the uterus or womb, the number is rising and the cancer has been linked with obesity and diabetes. Early detection gives women the best chance of survival, but as yet there is no screening programme anywhere in the world for endometrial cancer.
We want to explore the theory that the mix of bacteria or ‘microbiome’ present in a woman’s vagina and uterus can predict whether they are at high risk of having this cancer. Using samples from New Zealand women, we will confirm if certain microbiome signatures do predict risk. Then we will compare and select the best tools and methods that could be quickly picked up for use in healthcare testing by local laboratories. The results from this project will help us design a national endometrial cancer screening trial as well as boost understanding of the underlying causes of endometrial cancer.
Modelling Cooperating Mutations that lead to Acute Myeloid Leukaemia
Acute myeloid leukaemia (AML) is an extremely aggressive type of blood cancer with very poor survival rates – only 1 in 5 people diagnosed are likely to still be alive five years later. Blood cancer is caused by genetic changes and most patients diagnosed with AML have a mix of about 2-8 different genetic changes that contribute to development of the cancer. We know that the type and combination of genetic changes that a patient has will affect their overall outcome and survival. However our understanding of how the genetic changes affect survival, and our ability to develop new treatments for AML, is limited by the lack of research tools.
Through this project we will develop new laboratory models that will let us unravel the mechanisms by which different combinations of genetic changes work together and lead to blood cancer. We hope that these models will help boost our understanding of the biology of AML and enable future research on new drugs and strategies for the treatment of AML.
Hospice care delivery for patients with life-limiting illness inclusive of advanced cancer: Post-Covid-19 Gaps and Steps Forward
Cancer patients were identified as a vulnerable group during the COVID-19 pandemic. There was real concern about cancer patients with weakened immune systems being at increased risk of contracting COVID-19 and becoming very sick - especially before the arrival of vaccines. Also, advanced cancer patients have more unmet needs and challenges compared to early-stage cancer patients. To protect vulnerable patients during the pandemic, hospices restricted their visiting policies and scaled back community care delivery. This led to gaps in care to meet the physical and psychological needs of palliative care patients, including patients with terminal cancer.
At the same time, hospices and care providers developed many new methods, such as telehealth, to support patients despite the challenges. We want to understand the impacts of these policy and practice changes - both the positive and negative lessons learned – to improve care for future cancer patients, their families, and palliative care service providers. The project has two phases. Phase one is a telephone survey with representatives from hospices, partnering community groups, non-governmental organisations, and community care providers (GPs, district nurses), to discuss the challenges and responses to delivering palliative care during the pandemic. Phase two is group discussion with two groups of 6-8 participants from phase one. Participants will discuss ideas for new practices and organisational policies to increase the accessibility of hospice services.
A pathway to the discovery of new SHOC2 inhibitors for NRAS-mutant melanoma
New Zealand’s death rate from melanoma is the highest in the world. Recently, new drugs have become available here, and that has improved survival for many melanoma patients. But for about 20% of melanoma patients, that have mutations in a gene called NRAS, there are very few treatment options, so their cancer is likely to be fatal. We have discovered that if melanoma cells have the NRAS mutation, they are dependent on another gene called SHOC2 for survival. This dependence on SHOC2 makes it a good potential target for new drugs to treat NRAS-mutant melanoma. In this drug discovery project, we will look for new compounds that inhibit SHOC2. First we will set up a cellular assay that will tell us if a compound can inhibit SHOC2 from working. Then we will design new inhibitor compounds using computer models and test these in our cellular assay. This project is the first step toward our goal of making new drugs to treat NRAS-mutant melanoma.
Advancing genetic health: Mapping mRNA splicing of high-risk ovarian cancer susceptibility genes
Advances in cancer genetics means clinicians can now use genetic tests to diagnose individuals who are at increased risk of ovarian cancer. Some genetic changes are present in the ‘germline’, which means they are passed on from parent to child. Knowing which genetic variant is involved in a person’s cancer helps clinicians choose the right treatments for their patients, but interpreting genetic test results is a major challenge.
Our project will focus on non-BRCA breast/ovarian cancer susceptibility genes. We will use state of the art nanopore sequencing to build a comprehensive map of eachgene. Our data will be used to help developgene-specificvariant classification guidelines so that inthe future clinicians will have the tools to make better decisions for their patients. As members of international expert panels tasked with improving diagnostic guidelines for clinical and research laboratories around the world, our results will have both national and international significance.
Development of a novel growth hormone receptor antagonist and its application in hepatocellular carcinoma
Liver cancer is the fastest rising cause of cancer death in New Zealand. It isan aggressive and difficult to treat cancer. New treatments are needed, especially for patients with advanced-stage disease who currently have limited options.
Liver cancers with higher levels of growth hormone are linked with a lower chance of survival for patients.We know that using a drug to block growth hormone function slows the growth of liver cancer in mice. Recent testing of this same drug in two patients with advanced livercancer stabilised theircondition. Wehave discovereda new candidate drug that is better at blocking growth hormone in the laboratory. This project will test whether our novel drug is better at blocking liver cancer growth and progression, which is essential information before considering clinical trials.
Psychosocial Oncology New Zealand (PONZ) and Oncology Social Work Australia New Zealand (OSWANZ) are non-profit organisations dedicated to supporting health professionals working, within oncology services in Australasia, to strive for excellence in the psychosocial care of those affected by cancer. We aim to promote the importance of the psychosocial needs of patients and their support networks as an integral part of their health care journeys. This conference provides an essential role in connecting health professionals within the psycho-oncology space, enabling learning, collaboration and developing networks across the psycho-social community.
AGITG is a multidisciplinary collaborative group with a focus on gastrointestinal cancers. The Annual Scientific Meeting (ASM) provides opportunity for involvement and engagement in clinical trial development and the scientific activities of AGITG. The theme of the 2023 ASM is "equity, diversity and inclusion in clinical trials", recognising the need to increase equity of access for people from culturally diverse backgrounds, including Māori. Associate Professor Paringatai and Kahurangi Tipene are members of the AGITG Translational Research Committee, providing expertise in te ao Māori. Support from the CRTNZ will allow them to attend the ASM enabling them to share their knowledge in person.
This funding will sponsor Prof. Arie Perry, Professor of Neuropathology, University of California, San Francisco, to be the keynote speaker at the ANZSNP Annual Scientific Meeting in August 2024. Professor Perry is a world expert in brain tumour diagnostics. He will update New Zealand pathologists on the incorporation of testing into brain tumour diagnosis and improve accuracy of brain tumour classification in New Zealand patients according to international standards. Co-badging with Australasian Winter Conference for Brain Research (AWCBR) provides the opportunity for researchers in NZ to participate in the event. The conference will also attract delegates from Australia and Asia- Oceania region, providing opportunity for regional collaboration.
Presenting a workshop at the Lowitja Institute International Indigenous Health and Wellbeing Conference 2023
Travel to attend EMBL: Cancer genomics conference in Germany and visit LMB laboratory in UK
Presentation of a keynote talk at the 5th International Caparica Conference in SPLICING 2023 in Caparica, Lisbon, Portugal in July 2023, followed by laboratory visits with collaborators in Germany and UK.
Funding to travel to, and present at, the European Society for Oncology (ESMO) World Congress on GI cancer, and meetings with collaborators at Imperial College London.
Funding to attend PONZ (Psychosocial Oncology NZ) and OSWANZ (Oncology Social Work Australia and NZ) conference.
Registration and travel expenses to disseminate research findings at the 14th International Academy of Health Preference Research conference in Sydney.
Attendance at the World Indigenous Cancer Conference, March 2024, Melbourne, Australia
Collaboration and information gathering visits to clinical trials units/organisations in UK, Ireland and conference attendance in the US to plan, prepare and position cancer trials in the new clinical trial infrastructure changes in NZ
Attendance at the 21st Annual European Neuroendocrine Tumour Society Conference
Attendance at the 19th International p53 workshop, Trieste, Italy
Travel to attend European Association for Cancer Research (EACR) - Goodbye Flat Biology: Next Generation Cancer Models in Berlin, Germany
Leveraging AI to Explore Breast Density and its Implications on Māori and Pacific Women's Health in Aotearoa New Zealand
Breast cancer is a major health concern that often goes undetected until it's too late, particularly among Māori and Pacific women in New Zealand. Our new research project aims to change that by using advanced Artificial Intelligence to analyze mammograms more precisely. The focus is on 'breast density,' a factor that can hide cancer from traditional screenings.
Our team will use AI algorithms to look at historical mammogram images, giving us a better understanding of breast density patterns in Māori and Pacific women. This will help us determine who is at higher risk of breast cancer and needs more regular check-ups. We’ll also be validating our AI tools rigorously to ensure they are fair and accurate for all ethnic groups. The goal is to catch breast cancer earlier, which could mean less invasive treatments and better survival rates. This work will serve as a foundation for future research in personalized cancer screening. We're not just creating new tech—we're doing it in a way that embraces Manaakitanga, making sure everyone has an equal chance at life-saving early detection.
BARD1: a new prognostic marker for triple negative breast cancer
Triple-negative breast cancer (TNBC) accounts for up to 20% of all breast cancer cases. For nearly half of all TNBC patients, their cancer will spread, frequently to the brain. Notably, for TNBC patients the spread to the brain happens earlier than in other breast cancers, which reduces both quality of life and life expectancy. Sadly, once the cancer has spread to the brain treatment options are limited, have severe side effects, and often only give minor improvements in overall survival.
We know that the BARD1 gene codes for a protein needed for cells to function correctly. However when cells produce large quantities of some variant forms of BARD1, it results in cancer development and progression. Our early results suggest that 5-10% of TNBC patients will have a variant form of BARD1 that alters cell function and increases the chance of metastasis to the brain and central nervous system.
Identifying patients at high risk of brain metastasis remains challenging. We will use state-of-the-art technologies like gene editing and next-generation sequencing in combination with molecular cytogenetic screening to unravel how BARD1 to unravel which variants of BARD1 lead to brain metastasis
A novel type of cancer biomarker: detection of the inactive amyloid protein state of p16
A new class of anti-cancer drugs called CDK-inhibitors has recently entered the international market and PHARMAC funds these drugs for specific breast cancer treatments in Aotearoa New Zealand. These novel compounds are highly efficient and greatly expand our ability to treat this deadly disease. Nevertheless, only about one third of patients respond positively to this drug treatment and unfortunately, there is no predictive measure of which patients will benefit. The drug is highly successful because it replaces a natural protein called p16, that is often modified in cancers. We recently discovered that this protein can form amyloid-like structures, similar to those frequently found in neurodegenerative diseases. We found that p16 is no longer active when in the amyloid state but current clinical tests can not distinguish the functional protein from the inactive amyloid state. In this project, we will screen for the presence of this inactive amyloid state in a range of breast cancer samples. Knowledge about the p16 protein state will likely provide a long-sought predictor for CDK-inhibitor treatment success and this study may pave the way for a simple predictive method. This could improve successful application of the drug and lead to the application of these novel drugs in other cancers.
A gene expression-based prediction model for perturbation response in Head and Neck Squamous Cell Carcinoma
Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer and it is associated with poor survival. Despite efforts to use genomics and the development of potentially promising biomarkers, to predict and treat HNSCC there has been little benefit to patients over the past thirty years. The challenge is that with so many different possible gene-gene interactions, it is impossible to do all the experiments switching them on and off or testing outcomes to novel combination therapies. We need a model that can predict what is likely to happen when a gene is switched on or off – this could help to guide treatment choices, drug discovery, and cancer vaccine development. The focus of this project is to develop an artificial intelligence (AI) model using publicly available data for HNSCC. The model will use deep learning algorithms to predict gene expression responses so we can identify promising treatments to halt or reverse HNSCC progression.