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.
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.
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
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.
Developing Novel Molecules To Down-Regulate Src Family Tyrosine Kinases
Funder
National Health and Medical Research Council
Funding Amount
$201,261.00
Summary
Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling ....Leukaemia and cancer cells have altered biochemical properties resulting in their high rate of growth compared to normal cells. One of the common biochemical characteristics of cancer-leukaemia cells is augmented activity levels of enzymes called tyrosine kinases. A major group of tyrosine kinase involved in several cancer-leukaemia types is called the Src family of tyrosine kinases. One member of this family called Lyn has been our focus of study for several years, investigating the signalling pathways that it is involved in. This molecule has also been implicated in several specific leukaemia (Chronic Myeloid Leukaemia and Acute Myeloid Leukaemia) as well as cancer (Prostate, Colon, Breast) in recent years. We have identified a novel mechanism of down-regulation of this enzyme mediated by an adapter molecule called Cbp, which recruits the Lyn inactivating molecules Csk-Ctk as well as SOCS-1; together they inhibit the activity of Lyn and degrade the enzyme. Using our knowledge of the essential interaction elements of Cbp we will design and test various mini-Cbp molecules for their ability to inactivate and degrade Lyn in leukemic and cancer cells. These molecules may allow us to develop novel therapeutics capable of inactivating-degrading specific tyrosine kinases in cancer and leukaemia.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.
Characterisation Of CBF Acute Myeloid Leukaemia By MicroRNA Profiling
Funder
National Health and Medical Research Council
Funding Amount
$118,956.00
Summary
Recent studies have demonstrated the existence of small pieces of previously undescribed genetic material, known as microRNAs (miRNAs), which are thought to have critical functions across various biological processes and regulatory pathways in cells. This project aims to examine the role of these miRNAs in the development of abnormal cellular proliferation that leads to leukaemia, by examining the expression of all known miRNAs in the abnormal cells of our patients with leukaemia.
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.