2008 Grant Recipients
$1,050,000 INVESTED IN CANCER RESEARCH PROJECTS
Dr John Allen, Centenary Institute
Supported by Blackmores Three Island Race
Predicting response to proteasome inhibitors (myeloma -
bone marrow leukaemia)
Multiple myeloma is a common
cancer of the white blood cells called plasma cells, that secrete
antibodies to fight infections. Although the majority of myeloma
patients respond to chemotherapy, they invariable relapse, and the
relapsed disease is often drug-resistant. Some patients can be
cured by bone marrow stem cell transplantation but that is a
rigorous procedure and the majority of patients so treated also
relapse. If successful, this work will also point to new targets
for more effective, less toxic drugs for myeloma and enable
clinicians to optimise combinations with existing drugs.
Dr Anthony Cesare, Children's Medical Research Institute
Supported by Brett Levien Foundation
Preventing cancer cell growth by restoring normal
chromosome capping function (understanding the genetics of
cancer).
Human cells possess linear chromosomes
whose ends are 'capped' by physical structures termed
"telomeres". We believe that by understanding the nature of
telomere dysfunction in tumours we will gain valuable insight into
basic telomere function in healthy cells, specifically how normal
human cells regulate homologous recombination at their chromosome
ends.
Professor Maurice Eisenbruch, University of Sydney
Supported by Can Too
Understanding barriers to effective cross-cultural
communication about prognosis of metastatic breast and other
cancers
This project aims to provide information that
can be taken to train doctors to be more responsive to cultural
differences when they communicate with patients with advanced
cancer. In addition to research currently being conducted on
Chinese and Arabic-speaking patients, this project will focus on
Greek-speaking patients and how discussions between cancer
specialists and patients vary according to the cultural background
of the patient. Discuss how patients would prefer to be told about
prognosis and compare this to how doctors and community members
feel about discussing prognosis.
Dr Susan Fanayan, The Australian Proteome Analysis Facility
Supported by Can Too
Significance of MAL2-MUC1 interactions and
identification of other novel MAL2 binding partners in cancer by
proteomic approaches (understanding cancer behaviour using
proteomic approaches).
While increased MAL2
expression in different cancers has been reported by numerous
studies, little is known about how this increased MAL2 expression
may advantage cancer cells. This study will investigate the
significance of MAL2-MUC1 interactions in cancer and attempt to
identify other novel MAL2 binding partners to elucidate the
functional significance of increased MAL2 expression in cancer.
Dr Anthony George, University of Technology
Supported by Christmas Card Sales 2007
Computational design of inhibitors of P-glycoprotein
(resistance to chemotherapy)
P-glycoprotein, a normal
human protein, protects organs and tissues from metabolic and
dietary toxins; by binding toxins at the cell membrane and pumping
them out for excretion via the liver and kidney. Unlike most
proteins or enzymes that recognise a single substrate in a "lock
and key" manner, P-glycoprotein is able to bind and export hundreds
of different compounds including all known anticancer drugs. The
only identified inhibitors of its activity are too toxic for human
use. Drug chemotherapy is a frontline treatment for cancers.
Cytotoxic drugs inhibit DNA replication and cell division,
arresting the growth of cancer cells and tumours. However, in over
50% of cancers, these drugs also interact with the P-glycoprotein
gene causing untrammelled expression in cancer cells, whose
membranes become lined with P-glycoprotein "sentinels", like troops
at the battlements of a castle. This drug impregnable barrier
enables cancer cells to divide and spread. Other heroic means of
intervention such as surgery or radiotherapy are often
ineffectual at this stage, resulting in high rates of
mortality.
Dr Viive Howell, Kolling Institute
Supported by Can Too
Ovarian surface epithelial carcinoma
modelling
Ovarian cancer is the most lethal
of the gynaecological cancers. The best defined overall risk factor
for ovarian cancer in families is mutation of the Breast/ovarian
cancer susceptibility gene 1 (BRCA1). However, additional changes
are also required for the development of disease. From this work we
hope to achieve new insights into the complex genetic events that
drive both the initiation and progression of ovarian cancer. In the
long term this work may lead to earlier diagnosis and increased
survival of women with ovarian cancer.
Dr Toby Hulf, Garvan Instute of Medical Research
Supported by Can Too
Epigenetic Deregulation of miRNAs in cancer (prostate
cancer).
MicroRNAs have been described as 'the
string theory of biology' with their ability to regulate a huge
number of genes. One area in which microRNAs may play a key role is
in the control of epigenetics - the heritable modification of DNA
without a change in its sequence. Prostate cancer in Australia is
increasing and is now the second most common cause of cancer
mortality in men, after lung cancer. This project aims to identify
microRNAs that are involved with prostate cancer and the epigenetic
changes commonly associated with disease progression. This will
enhance our understanding of the disease while providing possible
targets for diagnosis and potentially opening new avenues for
therapy.
Dr Patric Jansson, University of Sydney
Supported by the Denton Family Trust
Pre-clinical development of second generation DpT iron
chelators for treatment of melanoma
Identifying
molecular targets for the diagnosis and treatment of patients with
the aggressive skin cancer, melanoma, is of particular
importance as the prognosis of advanced melanoma is very poor
because it is resistant to most chemotherapeutic agents. We have
been developing novel potent anti-cancer chelators (binding drugs)
that target the essential nutrient iron (Fe) in tumor cells.
Dr Hugh Morgan, Royal North Shore Hospital
Supported by Can Too
The role of active demethylation in maintaining the
differentiation status of cells (control mechanisms in
cancer).
Cells contain thousands of genes which are
the instructions for how cells work in our bodies. When some genes
don't work properly, this can lead to cancer. Genetic mutations
involve changes to the gene which make them not work. But sometimes
having a working gene turned on at the wrong time, or turned off
when it is meant to be on can also cause cancer. This project will
assess whether the way embryos switch genes on and off also occurs
in developed cells, and whether this is a cause in the onset of
cancer. Understanding these processes will lead to better
prevention and treatment of cancer.
Associate Professor Lou Rendina, University of Sydney
Supported by the Brett Levien Foundation
The targeting of brain tumors by a new class of agents
for Boron Neutron Capture Therapy
Boron Neutron Capture Therapy (BNCT) is an experimental cancer
treatment that utilises a combination of non-radioactive
boron-containing agents and low-energy neutrons to destroy cancer
cells. Unprecedented results from our laboratory demonstrate that
certain types of boron drugs have the potential to selectively
target malignant glioma, a brain tumour that is extremely resistant
to all conventional treatment protocols. We now wish to investigate
the tumour uptake of these agents in animal brain tumours using the
non-invasive imaging technique of Positron Emission Tomography
(PET).
Dr Ronald Sluyter, University of Wollongong
Supported by Can Too
Issues relating to blood clotting
Blood
clotting is a serious and life-threatening problem in
people with cancer, particularly in those suffering cancers of
the pancreas, ovary, prostate, lung, gut and brain, as well as some
leukaemias. Improved knowledge about the clotting processes
associated with cancer may lead to better treatments.
Dr Catherine Suter, Victor Chang Cardiac Research Institute
Macquarie Group Foundation Cancer Fellowship 2008
Piwi RNAs as mediators of gene silencing in cancer
(cancer genetics)
The aim of this current research is
to better understand how common cancers arise, and with
understanding comes progress. Examining the role of retroelements
in gene silencing is a new way of thinking in cancer research, and
has the potential to open up new avenues for anticancer therapies
and cancer prevention strategies. In doing this research we hope to
obtain information that will ultimately lead to better treatments,
more sensitive diagnostic techniques to detect cancer in its
earliest form, and knowledge that may help to reduce the likelihood
of cancer developing in the first place.
Dr Shane Thomas, University of New South Wales
Supported by Can Too
Tryptophan metabolism and survival of human tumour
cells
Humans rely on various defence mechanisms to
destroy cancer cells. The immune system promotes the expression of
a protein that degrades the amino acid tryptophan in cancer cells
in an attempt to deprive these cells of an essential nutrient
leading to their destruction. However, certain cancer cells are
able to tolerate this protein and instead use it to their advantage
to protect themselves from the patients' immune system. This
project aims to understand how these cancer cells protect
themselves from this protein such that they are able to use it
to their advantage.
Dr Wayne Thomas, Children's Cancer Institute Australia of Medical Research
Supported by Can Too
Identifying and inhibiting the mechanisms of N-Myc
activation in brain tumours
Brain cancer is a leading
cause of death in children under 10 years of age, and the second
most common type of cancer in children. Medulloblastoma is the most
common malignant brain tumor in children, and begins in embryonal
cells which have persisted beyond birth in the base of the brain.
Our studies aim to identify how medulloblastoma begins by
studies of a cellular protein which accelerates the growth of
cancer cells, N-Myc. Understanding the role of N-Myc in
medulloblastoma will lead to better treatments for the disease and
eventually preventative strategies.
