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.
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.
The Use Of Minimal Residual Disease Detection To Improve Treatment Outcome In Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$316,650.00
Summary
Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Available evidence suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the c ....Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Available evidence suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the cancer burden is at a low level, has a high likelihood of improving patient survival. The failure to respond well to treatment is assessed by a novel molecular genetic technique developed in our laboratory that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. The major goal of this project is to conduct a clinical trial in which this testing procedure is used at an early stage of treatment, and patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. In addition, the project is also directed towards investigating a range of genes known to have a role in drug detoxification. A number of naturally occurring variations exist for these drug metabolising genes and there is evidence suggesting that specific variations or patterns may influence a cancer's response to treatment. We will therefore examine the genetic patterns present in a large cohort of leukaemias and correlate these patterns with response to treatment. It is anticipated that these studies will help define the most appropriate treatment strategies for children with leukaemia. This project therefore has major implications for the therapeutic management of children with leukaemia and has the potential of contributing directly to the improved survival of this most common of childhood cancers.Read moreRead less
The Use Of Minimal Residual Disease Detection To Improve Treatment Outcome In Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$374,625.00
Summary
Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Evidence obtained by ourselves and others, suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of altern ....Leukaemia is the most common childhood cancer, representing approximately 35% of all cases. Despite intensive therapy, the disease frequently recurs in the bone marrow and although children are classified into good and poor prognosis groups at diagnosis based on a number of criteria, relapses nevertheless occur in both groups. Evidence obtained by ourselves and others, suggests that early detection of poor treatment response in the otherwise good prognosis group, and the implementation of alternative therapy when the cancer burden is at a low level, has a high likelihood of improving patient survival. In this regard, we have recently developed a novel molecular genetic technique that can detect and quantitate very low levels of residual leukaemia with great sensitivity and specificity. This technique is ideally suited for use in the routine clinical setting, and as a result of this development, we have now established a clinical trial (ANZCCSG Study VIII) in which patients who have a bad result on this test, will be given more intensive treatment to see if this improves survival rates. A number of research questions will also be addressed in this trial including whether the level of residual leukaemia at the end of therapy is able to predict future relapse that would otherwise not be suspected. It is anticipated that the clinical trial will help define the most appropriate treatment strategies for children with leukaemia. This project, which is at the forefront of such studies worldwide, has major implications for the therapeutic management of children with leukaemia and has the potential of contributing directly to the improved survival of this most common of childhood cancers.Read moreRead less
MicroRNA Expression And Genome-Wide Epigenetic Analysis Of Paediatric Acute Lymphoblastic Leukaemia (ALL)
Funder
National Health and Medical Research Council
Funding Amount
$71,765.00
Summary
Acute Lymphoblastic Leukaemia (ALL) is one form of childhood leukaemia, the causes for which are unknown. Evidence suggests genome changes are associated with ALL, specifically epigenetic changes such as DNA methylation and microRNA dysregulation. We aim to investigate these changes associated with childhood ALL. We believe this will refine the current diagnostic measures, more accurately predict patients� treatment response, and detect the minimal residual disease during and after treatment.
Role Of Connective Tissue Growth Factor In The Pathobiology Of Lymphoid Tumours And Response To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$603,615.00
Summary
Leukaemia is the most common cancer in children and the improved cure rates are among the major biomedical advances of the past five decades. However, we still do not fully understand why leukaemia cells have a growth advantage. We identified the growth factor CTGF as being massively activated in leukaemia cells. The project aims to study the role of CTGF in bringing about the disease. Insights gained are expected to lead towards novel treatments for patients with leukaemia.
A Preclinical Model Of Relapse In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$573,515.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease. We also hope to identify markers that can be used to screen for patients at increased risk of relapse.
Glucocorticoid Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$394,721.00
Summary
Glucocorticoids are among the most effective drugs used in the treatment of many haematological malignancies, including leukaemia, lymphoma and multiple myeloma. However, the development of tumour cell resistance to these drugs remains a significant problem, and clinically relevant mechanisms of glucocorticoid resistance remain poorly understood. This project aims to define mechanisms of resistance to glucocorticoids and develop new drugs to reverse resistance.
Genome-wide Epigenetic Analysis Of Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$410,469.00
Summary
Of all cancers in children, Acute Lymphoblastic Leukaemia is the most common. To date, the causal mechanism(s) for leukaemia in children remain unclear. Although 5-year event-free survival rates are relatively high (up to 80%) it is still unclear why children expected to survive with a good prognosis, succumb to the disease. Therefore, there is still a need to further refine current diagnosis and prognosis parameters that will together lead to improved outcomes to children with leukaemia.
The Role Survivin And XIAP (X-linked Inhibitor Of Apoptosis Protein) As Biomarkers And Therapeutic Targets In Paediatric Acute Myeloid Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$294,218.00
Summary
I am a Paediatric Haematologist/Oncologist focussing on new treatments for childhood acute myeloid leukaemia. This study is examining the effects of conventional and novel therapies on two proteins that prevent cell death in acute myeloid leukaemia. The study will also develop clinical trials of new drugs targeting these proteins.