Targeted Inhibition Of Multidrug Resistance-associated Protein 4 (MRP4) As A Therapeutic Strategy For Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$602,503.00
Summary
We have shown that a high tumour level of the gene, MRP4, confers a particularly poor outcome in children with the aggressive cancer neuroblastoma. Our results suggest that MRP4 can drive the growth of neuroblastoma cells, and that it does so by removing from the cancer cell a compound that normally regulates key cellular responses including survival and differentiation. We will explore this, and will also test promising inhibitors of MRP4 with therapeutic potential, that we have developed.
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.
Targeted Inhibition Of Polyamine Synthesis For Treatment Of Childhood Neuroblastoma
Funder
National Health and Medical Research Council
Funding Amount
$576,605.00
Summary
The childhood cancer, neuroblastoma, frequently has a dismal outcome despite the use of intensive therapy. Polyamines are molecules that are essential for cell survival and these are increased in aggressive neuroblastoma. Using pre-clinical models, we have shown that inhibiting polyamine production can significantly delay neuroblastoma growth. This project aims to improve the overall efficacy of this treatment by targeting multiple steps in polyamine synthesis in combination with chemotherapy.
Improved Outcomes For Children With Cancer Through Improved Target Identification And Drug Discovery: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$6,394,247.00
Summary
The majority of children with neuroblastoma still die of their disease, and survivors have serious side-effects of cancer treatment. We aim to discover better therapies for children with this cancer, conducting clinical trials using existing and new drugs in novel combinations. We will also investigate novel ways of targeting neuroblastoma cells, and study possible prevention strategies for this and other embryonal cancers. This work will have application in other childhood and adult cancers.
More Effective Therapeutic Targeting Of High Risk Childhood Cancer: Neuroblastoma As A Model
Funder
National Health and Medical Research Council
Funding Amount
$6,601,220.00
Summary
Cancer is the commonest cause of death from disease in Australian children. Childhood neuroblastoma is a particularly aggressive cancer, for which new treatment approaches are urgently needed. The team aims to discover better safer therapies for children with this cancer, conducting clinical trials using new drugs and novel drug combinations. We will also investigate novel ways of targeting neuroblastoma cells and identify therapeutic targets in neuroblastoma-initiating cells.
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.
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.
Delineating Mechanisms Of Acquired Resistance To Kinase Inhibitors And Devising Novel Strategies To Combat Therapeutic Resistance
Funder
National Health and Medical Research Council
Funding Amount
$437,034.00
Summary
Kinase inhibitors are some of the most successful anti-cancer agents that have emerged in the last 15 years. However, tumors become resistant to these drugs after showing initial response. Understanding mechanisms through which cancer cells become resistant to these drugs will allow us to develop effective strategies to counter it and achieve sustained responses to cancer therapy. I propose to build a research program to systematically study these mechanisms to improve cancer therapeutics.
Clinicopathological Characterisation Of Male Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
Male Breast Cancer is an uncommon and poorly understood disease. Due to its low frequency, there is a paucity of studies with large numbers of patients. Our aim will be to establish one of the largest worldwide databases of Male Breast Cancer. This will allow us to more thoroughly investigate clinical, pathological and molecular characteristics of male breast cancer, improve treatment of these patients and potentially develop novel and innovative strategies for treatment of female breast cancer.
Companion Biomarker And Therapeutic Strategy Development For Pancreatic Cancer
Funder
National Health and Medical Research Council
Funding Amount
$121,031.00
Summary
Innovation of predictive and responsive biomarkers in pancreatic cancer (PC) is of paramount importance. This project contains two parts: 1. Circulating DNA. It has been shown previously that DNA released into the blood stream by cancer can be measured, its usefulness in PC will be assessed. 2. ROCK-I as a predictive biomarker. ROCK-I is a protein involved in cell motility. The ability for ROCK-I amplification to predict for response to ROCK-I inhibitors will be assessed in vitro/in vivo.