|Boston, USA & Otago University (Postdoctoral Fellowship)||1|
The role of oestrogen receptor β in cancer: the other receptor
Many tumours express high levels of oestrogen receptor alpha (ERα), and it is a well-known prognostic marker for various cancers thus provides an important target for therapy. The closely related beta subtype (ERβ) acts in opposition to ERα but its involvement in cancer is unclear. This project will investigate the molecular role of ERβ in breast, colorectal and ovarian cancer, with the aim to use ERβ as a novel biomarker for tumour classification and prediction of treatment response. Further understanding may also allow the development of ERβ-targeted treatments to help improve outcomes of existing therapies in cancer patients.
Attenuation of Immunosuppression to complement GBM Immunotherapy
Over the last three years we have developed anti-tumour vaccines that show some efficacy in eradicating intracranial models of glioblastoma multiforme. However, to achieve full eradication of existing intracranial tumors it was first necessary to remove a network of "regulatory" cells, which are induced by the tumour to deliberately suppress immune responses. It is now recognized that such regulatory cells are a general feature of cancer. We therefore propose to investigate a series of clinically approved drugs that can potentially deplete or alter the function of tumor-induced regulatory cells, which will be used with our vaccines to provide effective therapy.
Titania nanoparticle targeted theranostics for breast, colorectal and prostate cancer
Cancer is the leading cause of death in New Zealand that accounts for 29.4% of all deaths. Current cancer therapies are not targeted to cancer cells leading to side effects. The project aims to develop targeted-non invasive cancer therapy with significantly reduced side effects compared to existing therapies. In this project theranostics (i.e. diagnostics therapy) based on titania nanoparticles will be used for managing breast, colorectal and prostate cancer. Titania nanoparticles will be capable of targeted cancer cell death by producing reactive oxygen species inside cancer cells upon exposure to x rays and sonic waves.
Novel reporter genes and PET probes to image tumour-targeting microbes in vivo
A promising new strategy for cancer therapy is to use engineered viruses and bacteria that infect tumour cells far more efficiently than healthy tissue. However, there are risks inherent in administering an infectious microbe to a person who is already sick. To monitor whether infection is confined to the tumour we will develop nitroreductase imaging genes for labelling tumour-targeting microbes. Using standard hospital (PET scan) technology, together with established or next-generation PET probes, it will be possible to show where in a patient's body these genes are located; and therefore whether the labelled microbe is confined to the cancerous tissue.
A Randomised Phase III trial of Stereotactic Body Radiotherapy (SBRT) for early stage inoperable non-small cell lung cancer (NSCLC)
This study tests a new method of treating early stage lung cancer patients who decline or are not fit for surgery. This treatment uses very high precision radiotherapy called Stereotactic Body Radiotherapy (SBRT). The trial aims to determine if SBRT given in only three treatments over two weeks is better than current radiotherapy treatment given daily over six and a half weeks. New Zealand study patients will receive SBRT or standard radiotherapy treatment. This study will provide excellent evidence to guide New Zealand and international best practice and will enable us to gain valuable hands on expertise in using SBRT.
How an isoform of the p53 tumour suppressor causes hyperplasia and cancer
The tumour suppressor protein p53 is arguably the most notable defence that we have against cancer. Recently, several naturally occurring short variants (isoforms) of p53 have been identified that are elevated in human cancers. This suggests that one or more of these p53 isoforms might cause cancer, in contrast to the established functions of full-length p53. To test this, we generated the first mouse in the world that makes the equivalent of the D133p53 isoform of human p53 (D122p53 in mice) and have shown that it does cause cancer. This proposal investigates the molecular mechanisms underlying its cancer-causing ability, which could lead to new targeted therapeutics...
Targeting of Cytotoxic Moieties into the Tumour Using HSA as a Carrier
Currently applied chemotherapeutic drugs are often not selective for tumour tissue and cause therefore serious side effects. New compounds based on the metal ruthenium are considered as promising anticancer agents, and have the potential ability to attach to a macromolecular carrier present in human blood serum and be released selectively in tumour tissue. Within this project, such compounds will be developed and characterised, and their reactions and effects on human cancer cells will be assayed. This approach, by allowing accumulation of the anticancer active moiety in the tumour, should provide drugs with lower side effects.
Targeting signalling pathways to refine the generation of anti-tumour T cells
Immune T cells isolated from tumour patients can be cultured ex vivo to large number, and transferred back to the same patient to induce tumour regression and improved survival. However, the ex vivo activation conditions can have huge effects on the therapeutic effectiveness of the transferred T cells. We will use current knowledge to optimize the activation conditions and examine the effects of critical factors that are known to regulate the production of functional T cells on tumour suppression. This information will guide the use of T cell activation strategies to improve cancer therapy.
Identifying the optimal Selenium compound and dose for use in cancer patients
Selenium is a trace mineral commonly taken by people hoping to prevent or treat cancer. However certain types of selenium could be harmful, especially at the high doses that show promise in reducing side effects of radiotherapy or chemotherapy without reducing their effectiveness. It is important to know which form of selenium can be most safely used at higher doses and have the best effect. In this clinical research study we will compare the effects of three different types of selenium in people with prostate cancer and chronic lymphocytic leukaemia, looking at their safety and beneficial effects on the cancer.
A randomised phase II study evaluating potential predictive biomarkers in the treatment of metastatic pancreatic cancer
Cancer of the pancreas is more aggressive than many other cancers. Although it can be treated with chemotherapy, this does not always work. Therefore one should be as confident as possible that the right kind of chemotherapy is being used, before starting treatment. Earlier work suggests that the commonly used drug gemcitabine is more effective in pancreatic tumours that express the protein "human equilibrative nucleoside transporter 1" (hENT1), compared to those that don't. We will study the ability of hENT1 to predict benefit from gemcitabine in metastatic pancreatic cancer, relative to a commonly used drug combination, oxaliplatin and fluorouracil.
NF-kB signalling in glioblastoma cells exposed to high-dose ascorbate and radiation.
People with glioblastoma multiforme (GBM) have a very poor prognosis because this cancer is extremely resistant to radiation therapy. Radiation causes DNA damage, but GBM tumours respond by ramping up their damage repair pathways, making them essentially resistant to radiation. We have shown that high-dose vitamin C makes GBM cells more sensitive to radiation by causing more DNA damage than radiation alone, while inhibiting DNA repair. We hypothesize that high-dose vitamin C inhibits activity of the survival factor NF-kB, and when combined with radiation will prevent NF-kB from repairing DNA.
Novel Enzyme Targets for Brain Cancer Therapeutics
Two particular enzymes, PP2Cβ and p400 have been shown to associate with a brain cancer-amplified gene but we do not know their roles in cancer development. We will test if alteration of enzyme activities can change cell behaviour so that cancer cells are more susceptible to the current cancer therapeutics. Additionally by providing molecular understanding of critical regulators in brain cancer-specific gene expression, our studies will identify novel molecular targets and mechanisms for intervention strategies to kill cancer cells.
Cohesin: an Achilles heel for MYC-driven cancer?
Aggressive, intractable cancers frequently have too much of a notorious cancer-causing protein: MYC. Drugs that reduce MYC levels are highly desirable for cancer treatment, but their development depends on understanding how MYC is over-produced. We found that the protein cohesin is required for switching on the MYC gene, but exactly how it does this is unknown. We suspect that cohesin is needed for a crucial step in producing messenger RNA from the MYC gene, and our project will test this idea. The results could identify cohesin as a novel therapeutic target in tumours thriving on too much MYC.
Ovarian cancer and contraception
Over 250 New Zealand women are diagnosed with ovarian cancer and over 160 women die from it every year. Despite advances in treatment, long term survival remains poor, so finding out how to prevent ovarian cancer is important. While it is recognised that oral contraceptive use reduces ovarian cancer, not all women can use oral contraceptives. There has been little research on the effects of other contraceptive methods. It is important to investigate whether other contraceptive methods also have protective effects on ovarian cancer, especially as long-acting progestogen-only contraceptive use is increasing in New Zealand.
Melanoma Summit 2013: Genesis Oncology Trust Sponsorship
New Zealand health professionals will gather in Wellington on 5 April 2013 for the third national Melanoma Summit. The one-day multidisciplinary meeting will provide a unique and important opportunity to highlight recent developments and to identify priorities for action in New Zealand. The Summit programme features New Zealand experts, including overseas speakers recognised internationally for their contribution to melanoma control, and workshops on prevention, diagnosis, clinical management and research. New Zealand currently has amongst the highest melanoma rates in the world. This one-day Summit will provide an opportunity for health professionals working in melanoma control to come together and help reduce our world-leading rates
Development of a clinical research database template system
Cancer Trials New Zealand was established in 2003, with the aim of supporting and conducting cancer clinical research in New Zealand that is of particular relevance to New Zealanders. Part of the support we provide is a system for managing the data collected for the research. To ensure we obtain reliable answers to research questions, these systems need to meet high standards. Setting up a system for a new trial requires much time and effort. We wish to set up templates that will allow us to speed up this process, giving a cost-effective system for collecting high quality data.
Predicting patient outcomes using biological modelling for radiation therapy treatment plans
Head and neck cancer patients experience debilitating side effects from radiation and chemotherapy treatments, which significantly affects their quality of life. SABER™ is a new software tool that may better predict both tumour control and severity of side effects. SABER™ has yet to be tested clinically. This project aims to do so by applying this program to the treatment plans of head and neck cancer patients and evaluating their toxicities and survival outcomes over time. The results of this project will significantly contribute to predicting and therefore managing the side effects experienced by cancer patients undergoing radiation therapy treatment.
Clinical trials workshop at TROG ASM 2013, Wellington
Clinical trials are fundamental to the development of innovative interventions that treat cancer. Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research. Funding from this grant would support attendance by experienced faculty to present at the, one day Clinical Trial Management Workshop that will be held on the first day of the Annual Scientific Meeting of the Trans-Tasman Radiation Oncology Group (TROG) scheduled for February 2013 in Wellington.
Genesis Oncology Trust palliative care breakfast lecture series
In its 10th year, the Genesis Oncology Trust Lecture Series continues to provide an easily accessible palliative care education opportunity. Delivered via teleconference, the eleven lecture series is attended by an average of 430 people each month. Registered sites throughout the country participate in the series. Participant numbers have continued to grow with approximately 2590 people listening to the breakfast lectures to date in 2012 – an increase of 25% on last year. Thanks to the generosity of the Genesis Oncology Trust the lectures continue to be available without charge to registered participants. In 2013 we will also provide post lecture access to some materials via our website for those unable to attend live lectures.
To attend the Australia and New Zealand Gynaecological Oncology group (ANZGOG) Annual Scientific Meeting (ASM) will be held on 20-23 March at the Sofitel Gold Coast Australia
To attend the Trans-Tasman Radiation Oncology Group 25th Annual Scientific Meeting, 26 February – 1st March 2013, Te Papa Conference Centre, Wellington
To attend the 2nd ESTRO Forum in Geneva, Switzerland from 19-23 April 2013
To attend the European Society for Radiotherapy and Oncology (ESTRO) 2nd International Congress Forum, Geneva, Switzerland, 19-23 April 2013
To attend the European Society for Radiotherapy and Oncology (ESTRO) 2nd International Congress Forum, Geneva, Switzerland, 19-23 April 2013
To attend the Keystone Symposium "Immunological Mechanisms of Vaccination" conference in Ottawa, Ontario, Canada. From 13th-18th December 2012. Laboratory Visit: Michel C. Nussenzweig, Laboratory of Molecular Immunology, Rockefeller University, New York, NY, USA.
To attend a palliative care conference in Ireland in April 2013: ‘Death, Dying, Loss and Care – Social Experiences or Medical Events?' Limerick, Ireland from 24-26 April 2013