2006 Grant Recipients
$743,835 invested in cancer research projects
Dr Jeremy Henson, Children’s Medical Research Institute
Causes of cancer, leading towards improved drug
design
Some cancer cells grow indefinitely because they prevent shortening of their chromosome ends (telomeres) by activating Alternative Lengthening of Telomeres (ALT). Specific telomere binding proteins protect the telomeres and regulate their length, but the nature of their involvement in ALT is currently unknown. Dr Henson and his team have preliminary evidence that increasing the level of one of these proteins, TRF1, suppresses ALT. They will determine the effect on ALT of altering the TRF1 protein complex to facilitate future development of an anti-cancer treatment.
Dr David Lovejoy, Department of Pathology, University of Sydney
A new range of drugs
Iron is needed by cancer cells to enable them to grow rapidly. Researchers from this group have previously used metal-ion binding drugs to remove iron from cancer cells, thereby causing these cells to ‘commit suicide’. Cancer cells also require copper, which is incorporated into various proteins enabling cancer to spread around the body. This project will investigate if their novel iron-binding drugs also bind copper and whether, in mice, the spread of cancer can be prevented or reduced by these drugs.
Dr Tao Liu, Children’s Cancer Institute Australia
Neuroblastoma in
Children
Neuroblastoma is the most common solid tumour of early childhood with a cure rate of only 30 to 40%. This project aims to investigate the mechanism of a class of new drugs called histone deacetylase inhibitors and to investigate the efficacy of molecularly targeted combination therapy. The results from this study will provide better understanding of histone acetylase inhibitor-induced cytotoxicity and resistance, and the basis for clinical trials of a combination therapy.
Dr Mariana Brocardo, Westmead Millennium
Institute
Colon Cancer
This study aims to understand how a large multi-functional protein, APC, is able to move between different locations within a cell. Dr Brocardo recently discovered that a cancer therapeutic agent, taxol, causes an unexpected re-distribution of APC in cells. Taxol treatment caused APC to move into the cell nucleus, and this may be important both for our understanding of how APC works, and is also relevant to our understanding of the cellular response to a common clinically-used drug.
Mariana Brocardo was supported by Mulpha Norwest Limited.
Dr Ulla Simanainen, Department of Andrology, ANZAC Research Institute
Prostate
Cancer
This research will examine how the male hormone, testosterone, influences the growth of the prostate and its development of diseases. Testosterone acts on tissue like the prostate by combining with a protein known as the androgen receptor. This research is using new genetic engineering techniques in living mammals (the mouse) to remove the androgen receptor from different parts of the prostate. This will allow a unique view of how the prostate develops in conditions where testosterone stimulation is lacking in different parts of the prostate. This might help find new ways to reduce the risk of human prostate diseases, which develop following decades of exposure to testosterone.
Dr Gavin Chapman, Victor Chang Research Institute
Improved Drug
Design
Dr Chapman’s proposed work focuses on the Notch1 receptor. Notch signalling is a critical signalling pathway during development, and is involved in a number of cancers. Dr Chapman and his team have recently discovered that a modification termed tyrosine phosphorylation occurs to the Notch1 receptor and is required for proper signalling. Once they understand why Notch1 is tyrosine phosphorylated, it should be possible to design drugs that specifically inhibit Notch1 signalling and hence could be used to treat cancers that depend on Notch1.
Dr Angela Hong, Department of Radiation Oncology, Sydney Cancer Centre, Royal Prince Alfred Hospital
Head and Neck Cancer
Dr Hong’s ultimate aim is to determine whether human papillomavirus (HPV) wart virus is a marker of prognosis in head and neck cancers and whether the virus affects the response of tumours to radiation. The findings will guide decisions of the value of HPV testing in patient management and may eventually leads to tailoring of the radiation schedule based on the HPV status of the cancer. This should translate to better outcomes for patients with these cancers.
Dr Megan Hitchins, Department of Medical Oncology, St Vincent’s Hospital
Causes of Colorectal
Cancer
In bowel cancer, genes important in preventing cells from becoming cancerous have been paralysed by a chemical change called methylation. Methylation is normally used to switch off genes when they are no longer required. The DNMT3L protein directs this process in embryos, but is not normally present in adult cells. Intriguingly, Dr Hitchins has found this process in cancers. Dr Hitchins will investigate whether DNMT3L is responsible for switching the wrong genes off, causing the cells to enter a cascade that ultimately ends in cancer.
Megan Hitchins was funded by Can Too Run 2005.
Dr Ben Gu, Department of Haematology, Nepean Hospital (University of Sydney)
Lymphoma and
Leukaemia
MMP-9 is very important for normal immune cells and tumour cells to digest the basement membrane to migrate to inflammatory sites or invade tissues. The P2X7 receptor can be activated by ATP which is a natural compound released into an inflammatory area. Based on Dr Gu’s preliminary findings, this study will investigate the role of the P2X7 receptor in rapid regulation of MMP-9 release. This study will help understand the mechanism by which human lymphoid tumour cells spread through the body.
Ben Gu was awarded the Macquarie Bank Foundation Fellowship for 2006.
* Dr Gu was Cure Cancer Australia’s Young Researcher of the Year in 2003.
Dr Andrew Biankin, Garvan Institute of Medical Research
Pancreatic
Cancer
Pancreatic cancer is the fourth leading cause of cancer death in men and women in Western societies. Nothing, apart from surgery in a small proportion of individuals, gives any hope. A better understanding of the molecular pathology of pancreatic cancer will lead to significant advances in treatment with a substantial impact on patient outcome. This project focuses on understanding the role of retinoic acid signalling in pancreatic cancer in an attempt to define novel diagnostic and treatment strategies that may extend the successful use of retinoids, as seen in the treatment of leukaemia, to pancreatic cancer.
* Dr Biankin was Cure Cancer Australia’s 2005 Young Researcher of the Year.
