Plasma genomic biomarkers for New Zealand cancer patients.
The use of Blood based biomarkers are promising for the detection the early detection and monitoring of patients with cancer. I will generate new methods during my PhD to improve the sensitivity and accuracy of such tests. The implementation of such robust tests will lead to better management of cancer patients in New Zealand. Furthermore, the tumour heterogeneity study that will accompany this will help determine the suitability of these biomarkers in the clinic. These are improvements are essential if blood-based biomarker tests are to be successful in the clinic.
The role of SLC23A1 and SLC23A2 in 5-fluorouracil cellular uptake, and their interindividual variability in target tissues.
5-Fluorouracil is an important and effective chemotherapy drug often used to treat breast and gastrointestinal cancers. However, it can be associated with severe and sometimes life-threatening side effects in some patients, the cause of which is unknown in many people. We are investigating how 5-FU enters cells to try and determine whether abnormally high uptake of the drug might cause these toxicities. We have identified two transporters which we believe may also transport 5-FU. We aim to confirm the role these transporters in 5-FU uptake, and investigate whether some people have dangerously high 5-FU levels in their normal cells.
Factors influencing health seeking behaviours among two cohorts of patients diagnosed with colorectal cancer.
Bowel cancer affects over 3000 New Zealanders every year. It is the second most commonly diagnosed cancer in men and women and the second highest cause of cancer death, with over 1200 people dying from the disease every year.
Awareness of bowel cancer signs and symptoms among the general public is low. This can result in delays in diagnosis and starting treatment sometimes with devastating consequences. This study aims to explore why some people delay seeking help once symptoms occur so that new approaches can be developed to promote awareness of signs of the disease and encourage earlier help.
Can stimulation of human antigen presenting cells with TLR ligands improve their capacity to initiate a T-lymphocyte response to a vaccine targeting cancer?
PD-L1 is an important protein that protects normal cells from an excessive immune response. However, cancer cells over-express PD-L1 to evade the host immune system. How PD-L1 expression is regulated in cancer cells remains elusive. Understanding the mechanisms of how PD-L1 is regulated is important for predicting responses for anti-PD-L1 treatment and for developing new combinatorial therapies. We will perform cutting-edge DNA and RNA based analysis followed by functional studies in a panel of PD-L1 expressing and non-expressing melanoma cell lines to provide a clear picture of how PD-L1 expression is regulated in melanoma.
The role of vitamin C transporters in cancers.
The role of vitamin C in cancer treatment remains unresolved. In order to shed light on this clinical issue, we aim to characterise the transporter proteins that facilitate cellular uptake of the vitamin in three types of cancer, namely bowel, breast and kidney cancer. We will utilise human cancer cells grown in culture as well as clinical samples collected from cancer patients to measure the levels of vitamin C transporters and vitamin C. Our findings will add fundamental information to cancer research and may identify biomarkers to stratify patients in clinical vitamin C trials.
Unravelling immune complexity in colorectal cancer patients.
The immune response has been shown to be an important factor influencing patient survival in colorectal cancer. However, within the tumour itself, the immune response can consist of cells that support or inhibit tumour growth. New immune therapies are not as successful in colorectal cancer as others. We propose to use a new technology, mass cytometry, to study in detail the local immune response in tumours of people with colorectal cancer. We aim to find new and better targets for immune therapies.
Modifiable novel mechanisms for demethylating drugs in myelodysplastic syndrome.
Myelodysplastic syndrome, a common blood cancer of the elderly has few treatment options, one being the use of drugs that remove methylation from DNA. Removal of DNA methylation ultimately leads to death of the cancer cells. We have observed that the pattern of removal of DNA methylation by demethylating drugs is incompatible with the currently accepted mechanism. We will therefore study the mechanism by which these drugs exert their effects. We hypothesize that the efficacy and toxicity of these drugs, in the laboratory and in patients, will be affected by modifiable factors such as ascorbate levels and metal ion levels.
Cytomegalovirus and Epstein-Barr virus in breast cancer tissue samples.
Breast cancer is the most frequently diagnosed cancer, and leading cause of cancer death, in women worldwide. The causes of breast cancer are not fully understood, but previous research by the applicants suggests that late exposure to certain viruses (in adulthood rather than childhood) may increase breast cancer risk. This study will use an innovative approach to test breast cancer tissue samples for the presence of genetic material and ‘molecular fingerprints’ of these viruses. If there is a link between viruses and breast cancer it could lead to the targeted treatment or prevention of a significant proportion of breast cancer.
Selective targeting of DNA repair to improve radiotherapy.
Cancer cells use special DNA damage response (DDR) mechanisms to escape the full effects of cytotoxic chemotherapy and radiotherapy. DNA-Protein Kinase (DNA-PK) is one enzyme within the DDR which is crucial to repair DNA damage caused by radiotherapy and some chemotherapies. Currently, there are few selective inhibitors of this enzyme. We will design and prepare new inhibitors of DNA-PK and will explore how structure impacts on their activity and selectivity. We will identify new, potent and selective inhibitors of DNA-PK and explore their potential to enhance radiotherapy.
A critical appraisal and exploration of New Zealand cancer-related clinical practice guidelines.
Cancer-related preventive, clinical and palliative care should be informed by high quality, rigorous evidence-based clinical practice guidelines. This project will critically look at the quality of cancer-related guidelines in New Zealand. It will explore the experiences of guideline developers, funders and panel members. The results will have an impact at a national level for cancer prevention, screening, diagnosis, treatment and palliative care. The project will lead to better informed, more rigorous guideline development in New Zealand; with an emphasis on high quality, user-friendly outputs with clear plans to transfer new knowledge to health professionals, patients and their families.
Helen’s Story – the Film. Supply of DVDs to all NZ hospices.
A recent documentary film “Helen’s Story” will be available for loan or viewing at every hospice in New Zealand, thanks to a grant from the Genesis Oncology Trust. “Helen’s Story” tells the heart-warming story of Helen Ngahuia, a young mother with terminal cancer, the response of her teenage children, and the support of her multi-cultural whanau. There are many twists and turns in this uplifting tale – some of which you won’t see coming – that gives an intimate insight into what a hospice really does, and how love, family and whanau can get you through anything.
New Zealand One Day Concept Development Workshop.
The aim of this workshop is to help early career researchers develop their new ideas for cancer clinical research studies. Teaching includes how to turn an idea into a successful clinical trial, important elements of trial design, as well as small group discussions on the research ideas of the participants. The goals are to train early career researchers in clinical research methods and to increase New Zealand’s capacity in clinical cancer research.
Genesis Oncology Trust palliative care breakfast lecture series.
Now in its 13th year, the Genesis Oncology Trust Lecture Series continues to provide an easily accessible palliative care education opportunity. Delivered via teleconference, the lecture series is attended by approximately 400 people each month. Registered sites throughout the country participate in the series. Lecture resources are also available online, with over 1000 lecture downloads during the last 12 months. Thanks to the generosity of the Genesis Oncology Trust the lectures will continue to be available without charge to registered participants in 2017.
Speaker Sponsorship of 2017 Psychosocial Oncology New Zealand (PONZ) conference.
To attend the Australian New Zealand Gynaecological Oncology Group (ANZGOG) Annual Scientific Meeting 2017, 29 March to Saturday 1 April 2017 at the Grand Hyatt Hotel, Melbourne, Australia.
To attend European Neuroendocrine Tumor Society meeting in Barcelona, Spain, from 8 - 10 March 2017.
To attend the Keystone Symposium Conference “Cancer Immunology and Immunotherapy-taking a place in main stream oncology” at Whistler, Canada on the 19-23rd of March 2017