Using functional genomics to screen for novel synthetic lethal targets in NRAS-mutant melanoma
New Zealand and Australia have the highest incidence of malignant melanoma in the world. Ofparticular clinicalconcern are melanomas with mutations in the NRAS gene, which are associated with a poor prognosis and for which there are no therapeutic agents specifically approved. There is a clear need for new therapies for NRAS-mutant melanoma. Through this research we aim to identify the genetic vulnerabilities that are synthetically lethal with NRAS mutations using gene editing technology in parallel with next-generation DNA sequencing. These genetic vulnerabilities will potentially uncover novel drug targets to overcome the challenges of treating NRAS-mutant melanoma.
Bridging the gap between complex immunology and clinical cancer research in New Zealand
The immune system is an important component of the body’s anti-tumour response. Patients with high numbers of immune cells in a tumour are more likely to recover than those with low numbers. However, the anti-tumour immune response is incredibly complex, and until recently, it was difficult to analyseall ofthe cells and molecules involved at the same time. I will use new technology and data analysis techniques to study the full complexity of the anti-tumour immune response in cancer clinical trials in NZ.
LuCaS(Lung Cancer Surveillance) Study: surveillance models for non-curative lung cancer patients.
Lung Cancer is New Zealand’s biggest cancer killer and quality of life is a priority for patients. Treatment for lung cancer continues to improve survival rates for patients. Many patients go through periods of surveillance where they are monitored for signs of their disease returning. Current models of surveillance are not evidence based and tend to fit a medical model rather than be patient centred. This feasibility trial will look at how models could be changed to fit better alongside patient’s lives whilst still providing safe care.
How do cancer cells change their identity in response to targeted therapy?
Cancer treatment has been revolutionised by targeted therapeutics which act by blocking the pathways that drive cancer. However, despite initial dramatic results, relapse is inevitable and a major clinical problem. Recent studies have identified a rare population of drug-tolerant cells as being largely responsible for relapse. These cells evade therapy by changing their identityduring the course oftreatment, thus surviving to repopulate the tumour. In this research we will determine how drug tolerant cells change their identity during therapy. Understanding how cancer cells change their identity will allow us to turn off this switch, improving outcomes for patients.
Developing immunotherapies for metastatic oestrogen receptor positive breast cancer
Over three quarters of breast cancer patients diagnosed in New Zealand present with hormone-sensitive disease and are treated with anti-oestrogen therapy. Unfortunately, many develop resistance to this therapy and spread to other parts of the body leading to significant loss of life. Better treatments for these patients are urgently needed. Our previous work suggests that anti-oestrogen therapy may make tumours more responsive to treatment that stimulates the immune system. We plan to test whether immune therapies in combination with anti-oestrogen therapy can be effective against cancers that have metastasised to other parts of the body.
Investigation of the potential negative impact of proton-pump inhibitor (PPI) drugs on capecitabine pharmacokinetics
Many anticancer drugs cause heartburn and proton pump inhibitor (PPI) drugs are given to help these symptoms. Recent studies suggest that when patients are prescribed PPI drugs with capecitabine they have poorer survival. The reason for this difference is not known. One suggestion is that PPI affect the dissolution of the capecitabine tablet and decreases how much enters the body. We will undertake a study to assess whether PPI adversely affect the absorption of capecitabine in patients. By understanding how PPI interact with capecitabine we will help NZ oncologists decide whether it is appropriate to prescribe these drugs together
Tumour targeted therapeutics for the treatment of glioblastomaGlioblastoma, the most malignant of primary brain tumours in adults carries a dismal prognosis with survival period of 15 months and minimal treatment options. The front-line chemotherapy agent, temozolomide, is not effective in majority of patients due to the presence of treatment-resistant cells. Most other chemotherapy agents are unable to cross the blood brain barrier (BBB) for meaningful intervention. This project aims to synthesize novel tumour specific drug-dye combinations having enhanced BBB crossing properties. These compounds will be tested for anti-cancer activities in patient-derived tumour cells. We envisage these compounds will specifically accumulate in brain tumours with enhanced specificity.
Identification and validation of DNA repair pathway proteins for the development of chemosensitizers of Topoisomerase 1 inhibitorsTopoisomerases are enzymes that maintain the three-dimensional state of DNA in human chromosomes. Drugs called topoisomerase poisons interfere with the action of these enzymes, and damage the DNA of cancer cells, and these drugshave proven useful in clinical cancer treatment. Unfortunately, many cancer cells can repair the DNA damage caused by these poisons, making them resistant to treatment. We aim to develop new drugs that inhibit the repair of such DNA damage, thus restoring the ability of such topoisomerase poisons to kill cancer cells. We will also use these drugs to provide an increased understanding of the biology involved.
Utility of DNA-methylation profiling of WHO grade II meningioma as a prognostic biomarker: a retrospective feasibilitystudyThis multi-centre collaboration aims to bring cutting-edge neuropathological techniques to New Zealand, to contribute to the improved understanding of the behaviour of meningiomas, a group of brain tumours that are generally benign. However about 40-60% of them are predicted to have a more aggressive course, based on their microscopicappearanceand are usually treated with radiation following surgery. Newer technologies could more accurately identify which patients need radiotherapy. This would improve patient care, survival, and other outcomes while also avoiding unnecessary treatment for some patients.
The Volatile Anaesthesia & Perioperative Outcomes Related to Cancer (VAPOR-C)Trial.Alarge multicentre, randomised trial of inhalational volatile versus intravenous propofol anaesthesia with or without lidocaine analgesia to reduce cancer progression after surgery.
Each year 25,000 New Zealanders are diagnosed with cancer, with a large number undergoing surgical treatment under anaesthesia. Alarmingly, early evidence suggests that anaesthetic drugs used during surgery can affect cancer spread, patient survival and rates of chronic pain after surgery.
Recent studies show that traditional inhaled (volatile) anaesthesia impairs the body’s cancerdefensesystem, while more recent alternatives of propofol total-intravenous anaesthesia and local anaesthetic lignocaine infusion are immune protective and can improve outcomes after cancer surgery.We are conducting an international trial to identify if widely used anaesthesia drugs can improve disease-free survival in patients undergoing cancer surgery.
Cancer Research Trust NZ palliative care breakfast lecture series.
Thanks to the generous support of Cancer Research Trust NZ, Hospice NZ is delighted to present the Cancer Research Trust Palliative Care Lecture Series 2021 to healthcare professionals across New Zealand, free of charge.
Each month, over 400 people including registered nurses, general practitioners, social workers, counsellors,pharmacistsand healthcare assistants access a series of lectures delivered via audioconference. Topics cover a wide range of clinical issues such as cancer therapies, rehabilitation, Māori models of palliative care and bereavement support.
Hospice NZ would like to thank Cancer Research Trust NZ for their ongoing support to deliver this valuable education opportunity.
To undertake dissertation,Masters of NursingProgramme, University of Auckland
To complete Master of Social Work thesis in 2021 via Massey University: Advanced Research Methods
New Zealand One Day Concept Development Workshop 2021
This one-day concept development workshop helps clinicians and researchers early in their career develop their ideas for cancer research studies. Participants are asked to come with an idea for a clinical trial. Teaching includes how to turn this idea into a successful clinical trial, important elements of how to design a trial, as well as small group discussions on each of the individual participants’ research ideas. The goals are to inspire research interest in clinicians and researchers early in their career, train them in research methods, and to increase New Zealand’s capacity in clinical cancer research.