Funded projects

Bringing Clarity to Variants of Uncertain Significance in Cancer.

Precision oncology aims to improve outcomes for cancer patients by tailoring their treatment and management to the underlying biology of their individual tumour. However, this can only be delivered with a solid understanding of the biological effects caused by the genetic changes that occur in the tumour. Unfortunately, up to 40% of genomic alterations found in cancer are variants of uncertain significance (VUS), genomic changes for which little or no functional data exists. VUS are a major challenge to the delivery of precision oncology and there is a real and tangible need to address the biological uncertainty surrounding them. This project aims to address this need by developing standardised tests, reagents and tools to aid in the reclassification of VUS. Through this, we hope to have a positive impact on patient care either by removing uncertainty associated with benign variants or confirming the disease association of oncogenic ones, potentially opening up new treatment options where they exist.

Novel approaches to the treatment of diffuse gastric cancer.

Hereditary diffuse gastric cancer is a disease caused predominantly by inherited mutations in the CDH1-gene, leading to a high risk for development of stomach and breast cancer. In NZ, Māori are disproportionately affected. Our ability to monitor and detect this disease before it becomes advanced is imperfect; once advanced, survival is poor. Consequently, the only way to reliably prevent stomach cancer in carriers, is for their entire stomach to be removed. One promising alternative is chemoprevention, an approach in which drugs are used to prevent cancer development. This research focuses on using novel preclinical models to test candidate chemoprevention drugs.

Attendance at the British Gynaecological Cancer Society Annual Scientific Meeting 2023.

Attendance at Current Issues and Future Direction: Preventing Cervical Cancer 2022.

Investigating the complex role of myeloid cells in cancer in Aotearoa New Zealand, using a kaupapa Māori approach. 

Myeloid cells are immune cells that comprise a large portion of the immune tumour
microenvironment. They are highly plastic and heterogeneous - their role in tumour development
and progression remains unclear. Māori and Pasifika are disproportionately represented in cancer
mortality. For equitable outcomes for Māori in research, indigenous knowledge must be included. I
will intertwine two independent disciplines (mātauranga Māori, immunology) and use high-
dimensional cytometry technology to develop an immune signature to predict cancer patient
responses to therapy. This research will bridge the gap between clinicians and immunologists and
improve the lives of cancer patients in Aotearoa.

The impact of rare copy number variants as modifiers of BRCA1 associated breast cancer risk.

Women at high-risk of breast cancer are in need of new and effective prevention strategies. Traditional options for breast cancer prevention include risk-reducing surgery, however this strategy is unwanted by many women due to a variety of reasons, such as fertility and menopause concerns. Providing doctors with a non-invasive and easily accessible preventative therapy for women at high risk of developing breast cancer would have numerous benefits for the health system, and for the patients and their whānau. Based on our recent genetic discovery, we aim to investigate whether a drug used in oral contraceptives (ethinylestradiol) can be repurposed as a novel preventative therapy for women at high-risk of breast cancer. This innovative and potentially transformative study is a vital step towards the development of a personalised preventative treatment that lowers the risk of breast cancer in high-risk individuals, resulting in fewer breast cancer diagnoses.

Attendance at the Society for the Study of Reproduction (SSR) 2022 annual meeting in Spokane, Washington, USA.

PhD student to attend and present at the International Society of Extracellular Vesicles Annual Meeting in Seattle in 2023.

Travel to attend CYTO conference and visit Laboratories in Canada.

Head and neck cancer in New Zealand

There are several different types of cancer of the head and neck, such cancer of the tongue, parts of the mouth, and throat. Several common causes, such smoking and alcohol and associated with certain occupations, have been found for some cancers of the head and neck but for some other cancers the causes are less clear. HPV infection has also been identified as a contributor to some head and neck cancers but its effect on the development of cancer in the presence of other causes is not clear. HPV infection also appears to affect survival after diagnosis of some head and neck cancers. This study will elucidate the action of HPV infection on the development of head and neck cancer in the presence and absence of other causes and provide important information for the future prevention of head and neck cancer.

FaR-RMS: Frontline And Relapse study in RhabdoMyoSarcoma

Rhabdomyosarcoma (RMS) is a rare soft tissue cancer that is most frequently diagnosed in children. Many patients with localised RMS survive after intensive treatment with chemotherapy, surgery and radiotherapy. However, if the disease spreads or is particularly aggressive, the majority of patients do not survive. The Frontline and Relapse study in RMS (FaR-RMS) has been developed by world-leading clinical researchers from the European paediatric Soft tissue Sarcoma Group, and will enrol patients across the United Kingdom, Europe, Australia and New Zealand. FaR-RMS is a revolutionary, overarching clinical trial, designed to simultaneously examine multiple aspects of treatment to improve survival and quality of life for all RMS patients (newly-diagnosed and relapsed). Research questions include adding new agents to standard chemotherapy, extending maintenance chemotherapy, optimising radiotherapy, and identification of new genetic biomarkers. Importantly, the trial design will enable promising new agents to be rapidly incorporated as they become available, without the need to open a new trial each time. New Zealand participation in this ground- breaking international trial will offer children and adolescents the opportunity to be involved in the most comprehensive and ambitious program of research undertaken for RMS, and offers the best chance to improve outcomes for these patients.

ADjuvant tislelizumab plus chemotherapy after post-operative pelvic chemoradiation in high-risk EndometriaL cancer (ADELE): a randomised phase 2 trial

Endometrial cancer is the most common gynaecological cancer in NZ with high rates in Māori  and Pacific women. Hysterectomy is the standard treatment for this cancer internationally. Unfortunately, for women with advanced endometrial cancer, the cancer will come back despite having surgery, chemotherapy and radiation in 30% of women. If the cancer comes back, treatment options are limited. Better treatment is needed to stop the cancer coming back. 

Targeting the immune system with immunotherapy may help treat endometrial cancer. Based on evidence from other cancers, using immunotherapy earlier may help reduce the chance of the cancer coming back. This study will combine an immunotherapy drug called tislelizumab with the standard chemotherapy and radiation treatment used in this type of cancer. We will see if we can reduce the chance of the cancer coming back and also assess if the extra immunotherapy impacts how well these women live. 

This study will test for markers that may help us know which patients are most likely to benefit from immunotherapy. This will include special testing of the tumour sample from the original operation and blood tests. 

This study will be opened across Australia and at multiple sites across NZ including Auckland, Wellington and Whangarei. 

To attend a training course hosted by McGill University, Canada.

The sixth Melanoma Summit 2021

Travel support for Professor Cliff Rosendahl to attend the Summit. Professor Rosendahl is a Queensland primary health care practitioner recognised internationally for his work in the early detection of melanoma. He will attend the 2021 Summit to share his expertise and provide crucial learning opportunities to upskill those responsible undertaking skin checks.

Cancer patients living distant from cancer treatment centres face the additional burden of travel. While some surveys examining this issue exist, no research exploring people’s stories of the impact of travel for cancer treatment and supportive care had previously been undertaken in New Zealand. We are currently completing a small study exploring the impact of travel on people with cancer and their whānau living outside Dunedin in the Otago/Southland region. Preliminary findings indicate a range of impacts, both positive and negative, challenges and barriers associated with travel to access treatment and supportive care. While our findings are a useful starting point for understanding the issues, they are not necessarily transferable to other parts of the country. Building on the findings of our small study, the overall aim of this research is to better understand the impact of travel on people with cancer, and their whanau, in different geographical contexts in NZ. Our findings will help improve the rural cancer experience.