Structural And Biochemical Investigation Of The Bloom�s Complex, Defective In Bloom�s Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$184,661.00
Summary
Bloom�s Syndrome is a rare inherited disorder that results in greater than 90% risk of developing cancer by the age of 25. The gene that causes Bloom�s Syndrome, called BLM, protects cells from cancer-causing mutations hence affected individuals develop the same types of cancers as the general population, only much faster. We will investigate the properties of the BLM gene product and understand how it protects us from cancer, and may influence some forms of cancer treatment.
Breast cancer is the most frequent malignancy among women, with an estimated 1 million new cases per year worldwide. A family of enzymes known as protein tyrosine kinases (PTKs) are fundamental in the initiation and progression of tumour growth and they are frequently hyperactivated in breast cancer. This proposal will examine whether inactivation of the enzyme known as TCPTP contributes to PTK hyperactivation and tumorigenicity in breast cancer.
Melanoma Resistance To Combination BRAF And MEK Inhibition Is Driven By Reprogramming Of MAPK Signaling
Funder
National Health and Medical Research Council
Funding Amount
$745,082.00
Summary
Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK ....Until recently, patients with metastatic melanoma were treated with single agent chemotherapy drugs that produce response rates of less than 10%. New drugs targeting the mitogen activated protein kinase (MAPK) pathway have now shown significant activity, but nearly all patients treated with these new inhibitors eventually develop resistance and progress. This project utilises patient tumour samples to examine the mechanisms of resistance and ways of enhancing the targeted inhibition of the MAPK signaling cascade.Read moreRead less
New drugs targeting the immune system have dramatically improved the survival of melanoma patients. Nevertheless, 30-40% of patients responding to these new inhibitor will develop drug resistance. This project utilizes patient tumour samples to examine the mechanisms of acquired resistance to immune checkpoint inhibitors. This information will accelerate the identification of novel combination therapies to improve patient outcomes.
Manipulating Oncogene Addiction And Immunity In The Treatment Of Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
Melanoma is a major Australian health problem and a common cause of cancer death in young adults. Treatment of melanoma has been revolutionised in the last few years, but many patients fail to respond to new therapies or rapidly progress on treatment. This proposal examines the mechanisms that drive resistance to therapy and identifies markers predictive of clinical response. This approach will accelerate the development of new strategies and improve patient care by personalising treatment.
The development of tuneable materials to allow the three-dimensional printing of cells. New low cost three-dimensional (3D) printers and reagents will be developed during this project to allow cancer biologists to print cells and polymers as more realistic 3D tissue models for biological assays. Such technology will be important for performing basic research into cancers as well as for providing better tools for drug testing.
Role of endocytic mechanisms in mammalian cytokinesis. Cell division requires endocytic proteins and failed cell division can contribute to cancer. This project aims to understand how endocytic proteins function to complete cell division successfully and has implications for the development of chemotherapeutic agents to treat cancer.
The Pez-TGFbeta-miR200-ZEB1-2 Axis In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
A feature of late-stage cancer is metastasis - the dissemination of cancer cells to other tissues. Despite advances in treatment of primary cancers, metastatic disease remains the major cause of death in cancer patients. In metastatic cancers, the cells undergo a change that enables them to initially invade the surrounding tissues. We have discovered a novel regulator of the invasive process in tissue culture and this study aims to substantiate its role in breast cancer.
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.
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.