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.
The Nature And Significance Of Clonal Evolution In Human Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$665,420.00
Summary
Cancers can progress in patients by developing genetic changes that favor the growth, survival and spread of cancer cells. However, the rate at which genetic changes occur in human cancer is not known. This project will determine the degree and biological significance of genetic change in human melanoma by using a novel method of growing tumors from single cells and comparing genetic differences between them.
Investigating Signalling Pathways That Mediate Suppression Of Anoikis By Chemokine Receptors In Metastatic Breast Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$597,349.00
Summary
This research aims at understanding the "nuts and bolts" of the main killer in cancer patients - tumour metastasis. We will look for molecules that are specific to metastatic tumour cells that transmit signals from the cell surface to the cell "suicide" machinery and prevent metastatic cancer cell death.
Effects Of A Novel Hotspot Mutation Of Brm In Non-Melanoma Skin Cancer Development
Funder
National Health and Medical Research Council
Funding Amount
$92,314.00
Summary
Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transfo ....Australia has the highest incidence of skin cancer in the world. SWI/SNF, a yeast nucleosome remodeling complex, is known destabilise interactions in DNA. It is made up of 8-10 proteins, including a novel tumour suppressor Brm. There is some evidence that Brm acts as a tumour suppressor in skin cancer, but relevance of a recently found mutation in Brm is yet to be characterised. This project aims to identify the effect of this mutation, on cellular sensitivity to UV radiation and examine transformation to malignancy.Read moreRead less
Identifying Castrate-resistant Tumour Cells In Localised Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$573,047.00
Summary
This proposal addresses one of the most important challenges in cancer: what cell population ‘drives’ tumour progression, and how can it be effectively targeted? We will define the prostate cancer cells that survive androgen withdrawal therapy and investigate new ways to target them. Eliminating these important cells earlier in disease progression will lead to increased survival for men with prostate cancer.
The Role Of DNA Sensing In The Pathogenesis Of Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$633,704.00
Summary
Colorectal (bowel) cancer is a leading cause of death in Australia and worldwide. The ability of the body to detect DNA from damaged or dying cells in the gut is an important part of the healing process. This response also provides protection against colorectal cancer. In this project, we investigate how a DNA sensor prevents the development of intestinal tumours. This project will lead to new ways to fight cancer in humans.
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.
Strategies For Enhancing The Treatment Of Colon Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$590,785.00
Summary
Colorectal cancer is the third leading cause of cancer related death in Australia. Strategies to improve outcomes for these patients are urgently needed. This NHMRC SRF Fellowship will seek to identify new molecules in cancer cells which can be targeted to treat this disease, and to discover genes which can be used to improve patient response to treatment.
Real-time Optical Window Imaging Of AKT-FRET Biosensor Mice To Maximise PI3K/AKT Drug Targeting Within The Hypoxic Microenvironment Of Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$683,447.00
Summary
Inefficient drug response in solid tumour tissue is often a limiting factor in the clinical effectiveness of cancer therapies. Using cutting-edge imaging technology and 3D models that mimic the disease, we have mapped areas of poor drug response within distinct regions of tumours with low oxygen levels known as hypoxia. Here, we will specifically target factors limiting efficient drug targeting in these areas to improve the encouraging anti-cancer profile of AKT inhibitors in pancreatic cancer.
Role Of LncRNA IDH1-AS1 In Regulating C-Myc Driven-glycolysis And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$685,043.00
Summary
It is thought that understanding cancer metabolism will reveal vulnerabilities that can be exploited in the clinic. Indeed, compared to most normal cells, cancer cells utilise different fuels to sustain proliferation and to adapt to their environment. Herein we have discovered a molecular switch that regulates the key metabolic enzyme IDH1 and show this controls tumour growth. Given this switch may be active in 50% of cancers we anticipate our work will have significance to many cancer types.