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.
Identification And Characterisation Of Novel FLT3-ITD Co-operating Mutations
Funder
National Health and Medical Research Council
Funding Amount
$659,245.00
Summary
Acute myeloid leukaemia is a cancer of the blood and bone marrow. We have identified new genes that act with the known oncogene FLT3-ITD in myeloid disease. We will examine in detail how these new genes contribute to the development of AML. This will aid in the development of new therapies for groups of AML patients with these mutations.
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.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.
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.
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.
The Biology And Clinical Manifestations Of Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$440,583.00
Summary
I am a haematologist studying the biology and clinical manifestations of chronic myeloid leukaemia with particular reference to the dynamics of response to kinase inhibitor therapy and the causes and clinical management of suboptimal response and drug res
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
Translation Of Genomic Findings To Improve Outcomes In Patients With Myeloid Blood Cancers
Funder
National Health and Medical Research Council
Funding Amount
$1,913,403.00
Summary
Changes within the DNA of blood cancer cells are responsible for causing cancer, but also control the progression through various stages of blood cancers and regulate the response of patients to treatment. It is fundamentally important to not only understand these genetic changes at the molecular level, but also to use these findings to rationally design clinical treatments that target these genetic changes to improve outcomes for patients with blood cancers.
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