Mab Immunotherapies For Myeloid Leukemia Patients With Germline Or Somatic RUNX1 Mutations.
Funder
National Health and Medical Research Council
Funding Amount
$766,995.00
Summary
This proposal presents preliminary evidence and proposes to confirm that 2 cell surface molecules, CD11a (ITGAL) and IL3RA (CD123) are direct (probably repression) targets of RUNX1 in HSCs, and are dysregulated in RUNX1 mutated AML. Monoclonal antibody therapies that target these two surface molecules have already passed different clinical trial phases for different diseases. We plan to show these antibodies are effective in RUNX1 positive AML in preclinical models and then clinical trials.
Personalised Medicine Markers Of Anti-EGFR Antibody Therapy In Metastatic Colorectal Cancer: Accelerating Clinical Translation With Collaborative Meta-analyses Based On Individual-participant Data
Funder
National Health and Medical Research Council
Funding Amount
$300,953.00
Summary
When selecting cancer therapy we take into account ‘biomarkers’, biological cancer characteristics that predict treatment success. We will work with an international group, the Advanced Colorectal Cancer Database, to analyse individual patient clinical trial data. We intend to validate biomarkers used to select treatment with cetuximab or panitumumab. Cancer genes called KRAS, NRAS, PTEN, PIK3CA, EREG and BRAF will be examined. Our study will provide best evidence for personalised treatment.
Pushing AR Toward Better Outcomes In Breast And Prostate Cancers
Funder
National Health and Medical Research Council
Funding Amount
$998,754.00
Summary
Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives ....Breast and prostate cancers kill >6000 Australians each year. These cancers are strikingly similar, both driven by hormone receptors that have ‘gone bad’. Current therapies aim to eradicate the receptors. While often effective, therapeutic resistance is common and results in fatal disease. We aim to develop new, less toxic treatments that switch receptor behaviour from good to bad, without destroying them. This should improve quality of life, while preventing drug resistance and loss of lives.Read moreRead less
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
Cerebral Palsy (CP) is a devastating, common developmental brain disorder once assumed to be due to lack of oxygen at birth. Using our unique Biobank with DNA and clinical data from families with a CP child, we are examining the genetic origins of CP and how genes and risk factors in pregnancy contribute. We will use computer modelling and testing in animals and brain cells, to understand causes of CP and devise predictive, preventative and therapeutic strategies.
Determining The Prerequisites For The Achievement Of Treatment-free Remission In Chronic Myeloid Leukaemia To Facilitate The Development Of New Therapeutic Approaches With Curative Intent
Funder
National Health and Medical Research Council
Funding Amount
$1,318,775.00
Summary
Chronic myeloid leukaemia (CML) can usually be treated effectively with long-term tyrosine kinase inhibitor (TKI) therapy. Remarkably, rare patients who achieve excellent responses can stop treatment altogether without relapsing. Detailed studies of these patients in terms of their genetic background, the biology of their leukaemia and their immune response may help us understand how this is possible, leading to new therapeutic approaches to make treatment-free remission more widely achievable.
The Clinical Significance Of Sex Hormone Crosstalk In Estrogen Receptor Positive Breast Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$1,009,006.00
Summary
Breast cancer is mainly a disease in which the sex hormone estrogen stimulates uncontrolled growth. We have recently discovered that other sex hormones, including progesterone and androgen, can redirect the actions of estrogen in breast cancers to halt growth or make a tumour disappear. This study will examine the complex interaction between all three sex hormones to develop new, more effective strategies for treating breast cancer.
A Sequential Multiple Assignment Randomised Trial (SMART) Of Nursing Interventions To Reduce Pain Associated With Chemotherapy Induced Peripheral Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$713,418.00
Summary
Modern chemotherapy treatments can result in damage to the peripheral nerves, resulting in a condition called peripheral neuropathy. This condition is characterised by a range of sensory and functional changes that can cause pain and reduced ability to perform daily activities. This project will test various non-pharmacological pain management measures to determine if they are effective in improving the quality of life of patients who experience this problem.
How IsomiRs Expand The MicroRNA Functional Repertoire In Affecting Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$439,570.00
Summary
MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA var ....MicroRNAs function as regulators of gene expression. It is becoming appreciated that microRNAs are frequently expressed as variants with subtly different sequences. We find here that variation in one important cancer-associated microRNA, miR-222, promotes differences in the behaviour of cells expressing them. This work seeks to understand how microRNA variation confers such properties to cells, to identify the genes miR-222 variants regulate, and to examine how widespread it is that microRNA variation contributes to cancer.Read moreRead less
Targeting MicroRNA-driven Mesenchymal To Epithelial Transition To Suppress Prostate Cancer Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$741,831.00
Summary
Prostate cancer kills ~3,000 men per year in Australia. The development of metastasis is the major cause of prostate cancer-associated death and has limited treatment options. In this study, we will characterise the role of a group of molecules, termed microRNAs, in prostate cancer metastasis. We will also test whether targeting microRNAs using novel drugs termed antagomiRs is an effective strategy to inhibit metastasis and thereby improve prostate cancer mortality.