ALT-associated PML Bodies: Keys To The Biology And Treatment Of An Important Subset Of Cancers
Funder
National Health and Medical Research Council
Funding Amount
$813,614.00
Summary
Alternative Lengthening of Telomeres (ALT) is a molecular mechanism used by ~10% of cancers to sustain their relentless growth. ALT is common in sarcomas and brain tumours which are difficult to treat. ALT cancers contain nuclear structures called ALT-associated PML nuclear bodies (APBs) which may be part of the ALT machinery. This research will investigate characteristics of APBs and how they are formed, and will use this information to identify drugs to treat ALT tumours.
Engineering MYCN Models Of High-grade Serous Ovarian Cancer (HGSC)
Funder
National Health and Medical Research Council
Funding Amount
$797,478.00
Summary
The most lethal type of ovarian cancer, high-grade serous cancer (HGSC), can be divided into four subtypes based on gene patterns. One subtype involves a set of genes/proteins that, in their specific combination, result in activation of a pathway known as MYCN. As most HGSC start in the fallopian tube, we are using fallopian tube material to make new MYCN HGSC models to observe development in the earliest stages. We hope to generate new tests and treatments for this subtype of ovarian cancer.
Linking Breast Development To Bone Metastasis: Role For The Osteogenic Transcription Factor Runx2 During Breast Carcinogenesis
Funder
National Health and Medical Research Council
Funding Amount
$565,145.00
Summary
Bone is the principle metastasis site of breast cancer and represents a major cause of morbidity and mortality. Runx2 is one potential candidate gene mediating breast cancer metastasis. Using mice with altered Runx2 levels and breast cancer models, this study will examine the role of Runx2 in breast cancer bone metastasis. Identification of a single gene that controls both breast and bone would open a new area of breast cancer research and a new gene against which therapies could be developed.
Targeting Survival Pathways To Overcome The Resistance Of Human Melanoma To Treatment
Funder
National Health and Medical Research Council
Funding Amount
$332,123.00
Summary
Melanoma is a major Australian health problem. This is believed to be due to resistance of melanoma cells to cell death associated with inappropriate activation of survival signalling pathways. My previous studies have provided a number of insights into resistance mechanisms of melanoma cells to apoptosis. I wish to understand more fully the molecular basis of the survival signalling pathways, and to identify new therapeutic targets for overcoming resistance of melanoma to treatment.
Therapeutically Exploiting Non-oncogene Addiction And Defining Genetic Interactions For Disease Progression In A Preclinical Model Of Inflammation-dependent Gastric Tumourigenesis
Funder
National Health and Medical Research Council
Funding Amount
$624,960.00
Summary
Cancers of the stomach are often associated with chronic inflammation and represent a major health burden with little treatment options available. We propose to test whether drugs undergoing clinical testing for other diseases may have beneficial effects in a preclinical model of gastric cancer, and establish the genetic interaction required for gastric cancer progression. The study outcomes may highlight novel therapeutic opportunities for the clinic.
Cancer cachexia is a devastating disease characterised by skeletal muscle wasting and weakness. It impairs patient quality of life and accounts for >20% of cancer-related deaths. My work aims to identify factors contributing to the development of cancer cachexia. This insight will then enable me to test potential strategies to prevent the wasting seen in cancer patients to improve their quality of life and to reduce mortality.
Molecular Pathways Mediating The Anti-tumour Activity Of WIF1
Funder
National Health and Medical Research Council
Funding Amount
$462,342.00
Summary
Osteosarcoma is the most common bone cancer. Treatment often entails aggressive surgery with intensive chemotherapy, although one third of those diagnosed will still die from this disease. We have found that the molecule WIF1 can suppress osteosarcoma growth. In this project we aim to identify genetic modifiers of WIF1, potential WIF1 interactors and define active domains of WIF1 for the development of more effective targeted therapeutics for osteosarcoma.
Receptor Tyrosine Kinase Function As Molecular Target In Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$415,788.00
Summary
As molecular cell biologist and protein chemist my motivation for research is to tackle metastatic cancer, one of the principle health burdens of the 21 century. Over the next five years I will lead R&D programs with national and international collaborators that will generate new diagnostic approaches and insights in basic and translational research. These will allow us to develop anti-cancer drugs, which target several of the mechanisms that are active in metastatic cancers.
The Role Of Redox Regulation In Controlling The Oncogenic Function Of Eph Receptors
Funder
National Health and Medical Research Council
Funding Amount
$71,766.00
Summary
Reactive oxygen species (ROS) produced in cancers activate cell surface receptor signalling pathways that drive cancer progression. I will study links between ROS and receptor signalling in cancer cells, and inhibit signalling with ROS scavengers delivered in nanoparticles, targeted to receptor complexes with specific antibodies. These will include antibodies we raised against ADAM10, a protease associated with multiple receptor signalling pathways, to simultaneously inhibit these pathways.
Molecular Characterisation Of Serous Ovarian Cancer With Poor Clinical Outcome
Funder
National Health and Medical Research Council
Funding Amount
$532,136.00
Summary
Ovarian cancer is the 5th most common cancer in women, and most lethal gynaecologic malignancy. Despite aggressive surgery and multi-drug chemotherapy the majority of women experience recurrence and ~70% will succumb to the disease. This project will investigate two molecular subtypes of ovarian cancer previously identified by our laboratory to better understand mechanisms associated with poor treatment response.