Translational Research Program To Advance Clinical Outcomes In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$418,192.00
Summary
Five-year survival in acute myeloid leukaemia (AML) is only 27%, placing it amongst the worst-ranked cancers for clinical outcome. Improved patient outcomes will be achieved through implementation of a Translational Research Program to support novel agent drug testing, early-phase and randomised clinical trials and a national clinical registry to audit outcomes. New insights into leukaemic stem cell function and mechanisms of drug resistance will inform the design of future clinical trials.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Targeting The EGFR And C-Met Tyrosine Kinase Receptors In Myeloproliferative Neoplasms
Funder
National Health and Medical Research Council
Funding Amount
$607,559.00
Summary
We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can ....We propose that in the blood disorders called Myeloproliferative Neoplasms (MPN) there are important changes that affect the function of receptors expressed on the surface of blood cells. These changes will perturb blood cell production and may be able to be targeted effectively with drugs. We will test this using laboratory-based and mouse models of MPN, together with specific drugs that are currently in the clinic, and that inhibit the activity of the key receptors involved. This approach can be rapidly translated to clinical trial.Read moreRead less
GADD45A Promoter Methylation And Poor Prognosis In AML:mechanism And Clinical Significance
Funder
National Health and Medical Research Council
Funding Amount
$706,280.00
Summary
DNA methylation associated with the GADD45A gene defines an AML patient group with poor overall survival and limited treatment options. We will investigate the significance of this modification for the response of AML cells to chemotherapy and dissect the mechanism associated with this event. To translate these findings into the clinic we will test whether these patients are responsive to new agents targeting DNA methylation, and investigate survival of patients in a large independent cohort
Transposon Mutagenesis For Discovery Of Disease Causing Genes And Their Cooperative Interactions In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$659,302.00
Summary
The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help dev ....The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help develop new cancer therapies.Read moreRead less
I lead a research program to improve outcomes for patients with chronic myeloid leukaemia (CML). We aim to identify poor risk patients and test new treatment strategies to reduce adverse outcomes. In good risk patients we aim to reduce the need for lifelong drug dependency. Through a combination of clinical trials, innovative correlative studies, and strong scientific collaborations, my team will continue to improve outcomes for CML patients globally.
Characterisation Of A New Poor-Risk Sub-Category Of Chronic Phase Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination ther ....The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination therapy.Read moreRead less
Discovery Of New Targets For Therapy That Kills Non-dividing Cancer Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$375,828.00
Summary
I am a clinical haematologist that specialises in treating patients with a terrible form of blood cancer, acute myeloid leukaemia. Survival rates for this disease have not changed for 30 years and we now realise this is because we are not targetting the queen bee of the cancer - the cancer stem cell. In this project I am looking for cell markers that are only present in rare, truly latent non-dividing cancer stem cells effectively change a remission into a cure.
Investigating The Molecular Basis For Drug Resistance And Disease Relapse In Myelodysplastic Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$722,557.00
Summary
Myelodysplastic Syndromes (MDS) are a group of blood stem cell disorders that result in low blood counts and leukemia especially in the elderly. Azacitidine (AZA) is a drug that improves blood counts and delays progression to leukemia and is the treatment of choice. However, only half the patients treated with AZA ever respond and half of the responders relapse within a year. We will describe the origins of MDS and the basis for drug response, resistance and disease relapse.
Targeting Epigenetic Enzymes In Core Binding Factor AML
Funder
National Health and Medical Research Council
Funding Amount
$542,273.00
Summary
Acute myeloid leukemia (AML) is a devastating disease and there are ~900 new cases diagnosed annually in Australia. A subset of AML, called core binding factor (CBF) AML is more responsive to conventional chemotherapies than other AMLs however patients still relapse indicating a need for new therapies. We will use preclinical models of CBF AML to identify the proteins and pathways that these leukemias are “addicted” to in order to develop new treatment options for these patients.