This study will address the idea that cancer commonly involves a genetic pathway that is normally used by stem cells to proliferate in an undifferentiated state. We have evidence to indicate that this system is active in cancer cells and believe this could explain how cancer cells manage to divide rapidly in a primitive state. This project may bring a new perspective to the study of malignant transformation and has the potential to reveal multiple new targets for cancer therapy.
Integrative Bioinformatic And Experimental Approaches To Define Novel Roles For Genes That Typically Regulate Axon Guidance In Pancreatic Cancer Initiation
Funder
National Health and Medical Research Council
Funding Amount
$587,955.00
Summary
Early detection and intervention would have a dramatic effect on improving the outcomes for pancreatic cancer. This however relies on understanding how the cancer is initiated. New analysis of more than 100 tumours identified aberrations in genes that typically regulate how the nervous system is positioned during development. We want to use novel bioinformatic approaches and a unique experimental method with cells in culture to rapidly and accurately find out which of these genes drives a normal ....Early detection and intervention would have a dramatic effect on improving the outcomes for pancreatic cancer. This however relies on understanding how the cancer is initiated. New analysis of more than 100 tumours identified aberrations in genes that typically regulate how the nervous system is positioned during development. We want to use novel bioinformatic approaches and a unique experimental method with cells in culture to rapidly and accurately find out which of these genes drives a normal pancreatic cell to become a tumour cell.Read moreRead less
TARGETING A NOVEL DNA-DAMAGE SIGNALING PATHWAY TO TREAT GLIOMAS
Funder
National Health and Medical Research Council
Funding Amount
$97,783.00
Summary
Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to ....Glioblastoma Multiforme (GBM) is a high grade brain tumour for which current treatment modalities are inadequate. Tumour recurrence is almost inevitable and average life expectancy is measured in months. We have identified two proteins as potential therapeutic targets and demonstrated that depleting these proteins in vitro severely impacts on tumour cell viability. We will investigate the impact of targeting these proteins in mouse models of human gliomas and dissect the mechanism that leads to their upregulation in tumour cells.Read moreRead less
Targeting The Histone Methyltransferase DOT1L For The Therapy Of Myc-induced Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$356,127.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Pancreatic cancer is the fourth leading cause of cancer death in adults. In this application, we will define how a protein called histone methyltransferase DOT1L promotes cancer initiation and progression, and whether inhibitors of the histone methyltransferase DOT1L exert efficient anti-cancer effects against neuroblastoma and pancreatic cancer.
Identification And Characterization Of A Novel Long Intergenic Noncoding RNA For The Therapy Of Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$601,386.00
Summary
Neuroblastoma is the commonest solid tumour in early childhood. Survivors suffer from lifelong disabilities due to chemotherapy. In this application, we will define the role of gene amplification of a long intergenic non-protein-coding RNA in determining the biological effects of a neuroblastoma oncogene, and promoting neuroblastoma initiation and progression. We will also define the anti-cancer efficacy of therapies targeting the long intergenic non-protein-coding RNA.
Loss Of Cytostatic Regulation By TGF-beta During EGFR-driven Tumor Development
Funder
National Health and Medical Research Council
Funding Amount
$605,031.00
Summary
Growth factor and cytokine signalling networks control many aspects of cell behaviour such as proliferation, survival, migration, invasive capabilities, transformation and differentiation. In normal cells, these complex signalling pathways are tightly regulated. Alterations of these signals are often found to cause, directly or indirectly, tumour formation. Transforming Growth Factor-b (TGF-b) and Epidermal Growth Factor (EGF) signalling pathways are both independently implicated as key regulato ....Growth factor and cytokine signalling networks control many aspects of cell behaviour such as proliferation, survival, migration, invasive capabilities, transformation and differentiation. In normal cells, these complex signalling pathways are tightly regulated. Alterations of these signals are often found to cause, directly or indirectly, tumour formation. Transforming Growth Factor-b (TGF-b) and Epidermal Growth Factor (EGF) signalling pathways are both independently implicated as key regulators in tumour formation and as such they are potential therapeutic targets. However, while both pathways have been studied extensively, little is known about the cross-talk between the TGF-b and EGF pathways. This project will establish the generality of a new tumor signaling axis, namely EGFR-Stat3-Smad7-TGF-b in EGFR-overexpressing tumors. Practically, it will provide guidelines for the development of new approaches for treating effectively the EGFR-driven tumors.Read moreRead less
The Role Of Interleukin (IL)-27 In The Endogenous Anti-tumour Immune Response And The Use Of An IL-27 Agonist As A Cancer Therapeutic.
Funder
National Health and Medical Research Council
Funding Amount
$473,960.00
Summary
Our data in mice suggest that immune cell signalling protein, interleukin (IL)-27, enhances anti-tumour immune responses and slows growth of mammary tumours and carcinogen induced sarcomas. This project aims to test how IL-27 promotes protective anti-tumour immune responses and to develop a modified IL-27 protein that will be tested as a cancer therapeutic in mice. This will be the first study to examine IL-27 function using physiological tumour models and may provide proof of concept for a new ....Our data in mice suggest that immune cell signalling protein, interleukin (IL)-27, enhances anti-tumour immune responses and slows growth of mammary tumours and carcinogen induced sarcomas. This project aims to test how IL-27 promotes protective anti-tumour immune responses and to develop a modified IL-27 protein that will be tested as a cancer therapeutic in mice. This will be the first study to examine IL-27 function using physiological tumour models and may provide proof of concept for a new therapeutic strategy for some human cancers.Read moreRead less
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.
MicroRNAs And Their Processing Complexes Integrate ErbB-2 And AR Signaling Pathways In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$660,665.00
Summary
Prostate cancer is the most common cancer in men and is dependent upon signaling from male hormones (androgens) for continued growth. We recently identified some novel small RNAs (intracellular messengers), called microRNAs, that are likely to play important roles in the growth of prostate cancer cells. This project will evaluate the functional role of these microRNAs in human prostate cancer, as well as some other proteins involved in microRNA processing and may provide the foundation for new a ....Prostate cancer is the most common cancer in men and is dependent upon signaling from male hormones (androgens) for continued growth. We recently identified some novel small RNAs (intracellular messengers), called microRNAs, that are likely to play important roles in the growth of prostate cancer cells. This project will evaluate the functional role of these microRNAs in human prostate cancer, as well as some other proteins involved in microRNA processing and may provide the foundation for new avenues for therapeutic intervention.Read moreRead less
Determining The Tumour Suppressor Function Of The MCC Gene And Its Significance To Treatment Outcomes In Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
This project analyses the early stages of bowel cancer, where we have discovered a new gene defect. We want to determine how the MCC gene defect promotes tumorigenesis and how it affects treatment outcomes, by studying a novel mouse model of bowel cancer. This will determine which cellular functions are altered following loss of MCC in bowel tumours and if the MCC defect can be exploited to identify patients who would benefit from radiotherapy or specific chemotherapies.