Cellular targets and pharmacology of peloruside A
Peloruside A, a marine sponge compound, is being developed by Victoria University as an anti-cancer drug. Peloruside has a similar but distinct action to Taxol, a chemotherapeutic drug used to treat breast, ovarian and lung cancer. Peloruside works by binding to a cell's cytoskeleton and inhibiting cell division. Other targets of peloruside could play important roles in any side effects of treatment, and these secondary targets are being characterised. The metabolism and elimination of peloruside by mice and isolated cancer cells will also be examined. These findings will contribute to the development of peloruside as a future drug for cancer chemotherapy.
The role of cytoskeletal proteins in modulating TGF-beta tumour suppression in the prostate
Worldwide, prostate cancer accounts for one death every 4 minutes. In many patients resistance to treatment will develop. New treatments are therefore needed. The study will determine how proteins of the cell's "skeleton" help enforce the actions of a tumour suppressing agent that is secreted in the prostate. It will provide knowledge fundamental to the development of novel drugs to treat prostate cancer.
Discovery and improvement of anti-cancer enzymes from bacteria
This project aims to develop enzymes from bacteria that are able to activate non-toxic "prodrugs" into highly toxic anti-cancer drugs. These enzymes will be delivered to cancer cells by tumour-specific viruses, making them sensitive to the prodrugs. Because normal human cells lack these enzymes, there will be minimal side-effects in healthy tissue. As well as having the potential to target both dormant and rapidly dividing tumour cells, these particular enzymes will allow us to follow the progression and distribution of virus in the body - a vital safety control which has been lacking in previous cancer gene therapy work.
Gynaecological Oncology Clinical and Research Fellowships at Charing Cross Hospital, London and The Royal Marsden, London UK
Gestational trophoblastic tumours and ovarian germ cell tumours are uncommon gynaecological cancers that are potentially curable. Charing Cross hospital in London has the world's foremost expertise in this area drawing on the largest caseload of these tumours. The aim of this fellowship is to develop subspecialty skills and gain research experience which will contribute to care and improved outcomes for patients with these cancers in our community.
Overcoming tumour-induced immune suppression with indoleamine 2,3-dioxygenase (IDO) inhibitors for cancer therapy
A hallmark of cancer is its ability to evade the immune system. Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades tryptophan is up-regulated in many cancers and recent studies indicate that IDO is a key player in mediating tumour-induced immune evasion. By reducing tryptophan levels in tumours, (tryptophan starvation) this enzyme can inactivate the function of important immune cells. The ACSRC proposes to start a new drug development programme targeting IDO. We will be developing assay methods to test the efficacy of our new IDO inhibitors and will also screen tumours for two functionally related enzymes, Tryptophan 2,3-dioxygenase and IDO-2.
Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy with Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma: PORTEC-3
Chemotherapy drugs, such as cisplatin, paclitaxel and carboplatin, work in different ways to inhibit the growth of tumour cells. Radiation therapy uses high-energy x-rays to kill tumour cells. Giving chemotherapy and radiation therapy after surgery may kill tumour cells that remain after surgery. It is not yet known whether giving chemotherapy and radiation together is more effective than giving radiation alone, the current standard, in treating endometrial cancer. This randomised trial is studying chemotherapy and radiation therapy together to see how well they work compared with radiation therapy alone in treating patients with high risk endometrial cancer.
Does tumour burden affect the patient's ability to process chemotherapy?
This study builds on our previous work looking at how cancer may alter the way in which the body processes cancer drugs. Some chemotherapy drugs are metabolised (processed) in the liver by an enzyme called CYP2C19. The level of this enzyme varies from person to person and about 3% of people have a genetic change which makes them poor metabolisers. This may mean that in these people some chemotherapy drugs do not work well. We have recently shown that more than a third of advanced cancer patients have poor metabolism- due solely to the presence of the tumour. In this new study we plan to see if poor metabolism also occurs in patients at diagnosis of cancer and if there are any changes as the disease progresses. These changes in metabolism could influence how each patient responds to the drugs over the course of treatment.
Targeting a new pathway in MYC-driven cancer
Rad21 is a protein that helps to hold chromosomes together during cell division. We found a surprising new function for Rad21: controlling the production of a cancer-causing protein - Myc. In this proposal, we will investigate whether Rad21 and Myc really are partners-in-crime. Can Rad21 contribute to cancers caused by Myc? We'll look at this in normal and cancer cell lines. And just how does Rad21 control Myc production? We think the answer may lie in the DNA structure itself. Regulation of Myc by Rad21 is an unexplored pathway that may contribute to cancer. Ultimately, our work could lead to new cancer therapies.
Down-regulation of expression of MGMT in melanoma and sensitivity to temolozomide
Rhabdomyosarcoma is a relatively common tumour diagnosed in young children. Treatment is aggressive, involving chemotherapy, surgery, and radiation. For patients with advanced disease at the time of diagnosis, prognosis is poor with <25% of patients achieving long-term survival. Little is known about the molecular defects underlying embryonal rhabdomyosarcoma, the most common subtype of this tumour but recent scientific findings suggest that defects in a cellular signalling pathway called the "Ras pathway" contribute to the development of this tumour. This projects aims at the identification of these defects. If successful, these findings may improve the diagnosis, treatment, and outcome of patients.
The molecular basis for tamoxifen resistance in breast cancer cell lines
One million women worldwide are diagnosed annually with breast cancer, of which 65% have oestrogen receptor positive cancer. Tamoxifen is the efficient drug treatment for this cancer. However, one third of women develop resistance to tamoxifen during treatment and their tumours become more aggressive. Our research will concentrate on two breast cancer cell lines displaying varying degrees of resistance after exposure to tamoxifen. We propose to study the development of tamoxifen resistance developed in the cancer cell lines. We hope to extend our knowledge in understanding drug resistance in breast cancer and contributing to improved treatment strategies for breast cancer.
The Role of p53's Transactivation Domain in Tumour Suppression - A Proteomic Study
There is a molecular guardian (known as p53) that governs cellular responses to prevent damage in our cells, which could otherwise lead to cancer. The p53 molecule is very important for cancer prevention as it can destroy or repair damaged cells. Faulty p53 is found in most human tumours. Cancer therapies targeted to mend faulty p53 would be ideal, as would therapies that target other molecules that execute p53 responses. However, treatment strategies are limited until we understand exactly how p53 works. This project aims to identify molecules in the cell that respond to a specific region of p53, to understand why this region is key for preventing multiple tumour types.
Molecular mechanisms controlling melanocyte precursor populations in Zebrafish
Melanoma is an increasing health problem in NZ, despite public education programs to reduce sun exposure. Improved understanding of the biology of melanomas and normal pigmented cells (melanocytes) is urgently needed, to develop strategies to inhibit the formation of melanomas or to delay their progression. Zebrafish is a small fish with characteristic dark stripes running the length of the body. Zebrafish is a valuable animal model used to understand many human diseases including cancer. The aim of this project is to identify the cells responsible for re-growing the stripes following partial amputation of the tail fin. The results will provide essential information regarding stem cells and cancer treatment.
An extension of a pilot study of the pharmacokinetics of cyclizine, its main metabolite, norcyclizine and other metabolites in palliative care patients.
Nausea and vomiting are common in palliative care patients. The drug cyclizine often relieves these symptoms. It is broken down in the liver perhaps by the enzyme CYP2D6. The aim of this study is to maximise efficacy and minimise toxicity of cyclizine in palliative patients. Studying plasma concentrations of cyclizine and its break-down products and linking them to the patient's genetics of CYP2D6 may result in better therapeutic use of cyclizine via dose individualisation and thus improved outcomes. The qualitative interviews will enable clinicians to better understand how it feels for this population to engage in clinical research.
Purchase of specialist palliative care books, journals and manuals
Hospice Wanganui received a Certificate of Outstanding Achievement in 2004, for outstanding demonstration of best practice in optimising wellness and quality of life; and a Certificate of Accreditation on 15 December, 2007 - 14 December, 2010 from Quality Health New Zealand. (Which is the New Zealand Council on Healthcare Standards.) To continue to achieve these standards of excellence, Hospice Wanganui is applying to Genesis Oncology for a grant to upgrade our palliative care/oncology library with the latest books manuals/journals on education/professional development/cancer research/cancer treatment and relevant new information about palliative/oncology care for our medical doctors and nursing staff.
Genesis Oncology Trust palliative care breakfast lecture series
This is the sixth year Hospice New Zealand and the Genesis Oncology Trust will work together to provide the popular breakfast lecture series. The series is delivered via teleconference so is easily accessible for all hospices, DHB sites and individual members of Hospice New Zealand throughout the country. Lectures run for one hour on the first Thursday of the month from March - December. On average 270 health care professionals from the deep south to the far north listen to the various palliative care related topics each month. Thanks to the continued support of the Genesis Oncology Trust participation for registered sites is at no charge.
Assessment of the influence of timing of post-lumpectomy radiation therapy on local recurrence in early breast cancer.
If breast cancer is detected at an early stage, it is usually possible to treat the cancer with a combination of surgery, followed by radiation treatment. This enables the woman to retain her breast, which is important to many women. However, if the radiation treatment is delayed, it may lose some of its effectiveness and the cancer may re-grow. If this occurs, a mastectomy is needed. This project is looking at the cancer recurrences in NZ women who had delays in treatment due to staffing shortages in NZ in the past few years. If this demonstrates an increased risk of recurrence, this will help resource planning in the future. To date 2,150 women have been accrued to this retrospective study, which provides a large group to help answer this important question.
To attend and present at the 100th Annual Meeting of the American Association for Cancer Research (AACR), Denver, Colorado, April 2009
To fund dissertation that will complete a Masters in Health Sciences at the University of Auckland
To attend the 14th World Conference on Tobacco or Health (WCTOH) and the International Tobacco Control (ITC) project members meeting in Mumbai, India, March 2009
Breast Reconstruction travelling Fellowship in North America
Impact of obesity and insulin-resistance on response to chemotherapy in colorectal cancer
Rates of colorectal cancer and obesity are very high in New Zealand. Obesity has been implicated in worse colorectal cancer prognosis, but the impact of obesity on tumour response to chemotherapy remains unclear. In this study, the effect of obesity-related factors on the ability of tumour cells to resist chemotherapy treatment will be measured in cancer cell lines in culture. The impact of these factors and drugs on molecular pathways in cancer cells will also be investigated. This study will increase our understanding of how obesity-related factors affect patient response to chemotherapy and shed light on the molecular mechanisms involved.