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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.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.
Molecular Pathways Mediating Quiescence And Resistance In Leukaemia Stem Cells In Acute Myeloid Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$100,381.00
Summary
Acute myeloid leukaemia (AML) is a devastating cancer of the blood and bone marrow which is rapidly fatal unless effectively treated with chemotherapy. AML is caused by genetic events that alter normal blood stem cells to give them a growth and survival advantage and also may confer resistance to chemotherapy in some cases. We will evaluate and target the mechanism of this resistance in laboratory models. This information can then be used to design new treatments to improve outcomes in AML.
Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
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
Toward Effective Targeted Therapies For Acute Myeloid Leukaemia (AML)
Funder
National Health and Medical Research Council
Funding Amount
$551,345.00
Summary
Standard chemotherapy for acute myeloid leukaemia (AML) is highly toxic, and has not changed in over 40 years. We will conduct a world-first clinical trial incorporating ABT-199 (Venetoclax) to target BCL2 into the standard-of-care treatment for AML. A second initiative will explore the potential for small molecule inhibitors to simultaneously target both BCL2 and its related partner MCL1, to create a “chemotherapy-free” regimen for AML. These studies promise to herald a new era in AML therapy.
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
INTERCEPT (Investigating Novel Therapy To Target Early Relapse And Clonal Evolution As Pre-emptive Therapy In AML): A Multi-arm, Precision-based, Recursive, Platform Trial
Funder
National Health and Medical Research Council
Funding Amount
$5,789,515.00
Summary
Acute myeloid leukemia is a rare and lethal blood cancer with limitless potential to evolve resistance. New technologies allow early detection of molecular 'fingerprints' of returning disease. We propose an international research team to conduct a multi-arm, precision-based platform trial aimed at increasing and extending the duration of patient response and survival using novel combination options. INTERCEPT will suppress and eradicate relapse before the patient becomes clinically unwell.
New Compounds For Tailored Therapy Against MLL-rearranged Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$326,401.00
Summary
Some of the worst leukaemia survival rates are found in children and adults whose leukaemias display abnormalities of the MLL gene and alternative therapies are therefore urgently required for these patients. The aim of this project is to develop new compounds that specifically inhibit this abnormal gene and in turn inhibit the growth of these cells in the patient. In this way we hope to provide new and more effective therapies for patients affected with this aggressive type of leukaemia.
Targeting Leukaemia Stem Cells Through Inhibition Of Telomerase
Funder
National Health and Medical Research Council
Funding Amount
$651,979.00
Summary
Acute myeloid leukaemia (AML) is a type of very aggressive blood cancer that kills up to 1000 Australians every year. We use chemotherapy to treat AML, however, most patients are not cured by chemotherapy alone and the disease eventually comes back (relapses). We are looking at a new type of treatment for patients with AML that targets the genetic material (DNA) within the leukaemia cells. Our work has shown that this new type of treatment may prevent relapse after chemotherapy.