Triple negative breast cancer (TNBC) is an aggressive disease subtype that lacks targeted therapies. We have identified a protein associated with TNBC termed SgK269 that regulates the transmission of signals instructing the cell to grow and migrate. SgK269 associates with a closely-related protein termed SgK223 to form a signalling complex. The aim of this project is to characterise the role of this signalling complex in TNBC and determine whether it represents a potential therapeutic target.
Single-cell Optical Window Imaging In CDK1-FRET Biosensor Mice To Assess Tissue Stiffness And Optimise Delivery And Therapeutic Response To Gemcitabine/Abraxane In Pancreatic Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$676,979.00
Summary
Inefficient drug response in solid tumour tissue is commonly 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. Here, we pinpoint and specifically target key factors limiting efficient drug targeting in order to improve the encouraging anti-cancer profile of the new drug combination Gemcitabine/Abraxane in pancreatic cancer.
Biosensor Imaging In Preclinical Pancreatic Cancer Targeting: Taking Cancer Targeting To New Dimensions.
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Using cutting-edge imaging technology and 3D models that mimic cancer, we can map areas of poor drug response within distinct 'stages' or regions of tumours. Here, we pinpoint and specifically target key factors limiting efficient drug response in order to improve the encouraging anti-cancer profile of new or current drugs in pancreatic cancer.
Targetting Deregulated Signalling Pathways In High-grade Serous Ovarian Cancer: Defining Therapeutic Response And Mechanisms Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$641,263.00
Summary
Ovarian cancer is the major cause of death from gynaecological cancer. Most patients present with advanced disease and die of their cancer. This proposal aims to use new research detailing the common genetic changes in tumour samples and our extensive panel of ovarian cancer cell lines to identify new treatment options for specific types of ovarian cancer. We expect this will result in clinical trials of therapies selected based on the characteristics of an individual patient’s disease.
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.
Rad50 Protects The Integrity Of The Genome To Minimise Disease Risk
Funder
National Health and Medical Research Council
Funding Amount
$524,222.00
Summary
Exposure to both endogenous products of metabolism as well as a variety of exogenous agents (UV, X-rays) increases the risk of cancer and other diseases. This project is designed to further investigate a novel defect in the Rad50 gene that predisposes to genetic instability and cancer. In short we have described for the first time a patient with a defect in the Rad50 gene. This information will assist in understanding our defence systems against oxidative stress to reduce the risk of disease.
Evaluation Of Molecular Mechanisms Driving Metastasis Using Integrated Intravital Imaging
Funder
National Health and Medical Research Council
Funding Amount
$885,271.00
Summary
Metastasis is the leading cause of cancer-associated death. Understanding key steps that drive the spread of cancer is critical to improve current treatment strategies. Using cutting-edge imaging technology and 3-dimensional model systems that mimic the disease, we will pinpoint key events that are susceptible to drug intervention and identify new therapeutic targets.
Global Characterization Of The Src-regulated Kinome
Funder
National Health and Medical Research Council
Funding Amount
$591,334.00
Summary
This proposal aims to use new cutting-edge techniques to globally characterize the impact of a particular cancer-causing gene, or oncogene, on the expression and function of an important family of regulatory proteins, termed kinases, in cancer cells. This will identify proteins critical for cancer cell growth and survival that represent potential targets for therapy.
Identification Of Novel Treatment Strategies For Human Cancers Through Integrative Phosphoproteomics And Kinomics.
Funder
National Health and Medical Research Council
Funding Amount
$763,409.00
Summary
This proposal aims to use new cutting-edge techniques to characterize, at a global level, changes in growth regulatory signals in cancer cells. This will identify proteins critical for cancer growth that represent potential targets for therapy. In addition it will highlight ways to select the most effective treatments for individual patients. The ultimate outcome of this work will be improved treatment strategies for cancer patients, and hence reduced morbidity and mortality.
Studies On The Tumour-associated PIK3CA(H1047R) Mutation Using In Vitro And In Vivo Models Of Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
PIK3CA mutations are frequently found in breast and ovarian cancers but how they cause cancer is not clear. We will exploit a unique mouse model to investigate the functional effects of PIK3CA mutations in cells and their role in cancer development. Understanding the mechanisms by which PIK3CA mutations regulate cell function and drive tumour growth will allow the rationale design of novel anti-cancer agents that specifically target this important cancer pathway.