Downregulation Of N-myc Oncogene Expression As A Therapeutic Strategy For Childhood Neuroblastoma.
Funder
National Health and Medical Research Council
Funding Amount
$145,990.00
Summary
Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients ....Neuroblastoma is a common cancer of young children which, despite the use of powerful anticancer drugs that cure other childhood cancers, has only a 40% survival rate. Many laboratories have shown that the most aggressive neuroblastoma tumours, which are most resistant to the action of anticancer drugs, have an abnormal number of copies of a cancer-associated gene, called N-myc. Patients whose tumours have multiple N-myc copies have dismal survival prospects, and new treatments for such patients are urgently needed. Several studies, using models of neuroblastoma cells growing in the laboratory, have shown that it is possible to create small fragments of genetic material which can specifically switch off the N-myc gene. When this happens, the neuroblastoma cells behave in a less aggressive and malignant way. We have recently shown that these genetic fragments are capable of reducing the growth of tumours in mice which have been genetically manipulated to develop neuroblastoma. We now want to develop new types of genetic fragments (DNAzymes) that will be even more effective at switching off N-myc and inhibiting neuroblastoma development, because these fragments may be extremely valuable for treating neuroblastoma in patients.Read moreRead less
Accelerating Paediatric Cancer Precision Medicine With Mass Spectrometry-based Proteomics
Funder
National Health and Medical Research Council
Funding Amount
$79,041.00
Summary
The Zero Childhood Cancer (ZERO) Program measures the DNA and RNA in individual cancer samples and then recommends a unique treatment plan for each child. In this study, we will measure the proteome (ie the set of proteins) in ~100 ZERO cancer samples at the Children's Medical Research Institute's ProCan. The goal of this project is to assess the value of protein data for informing drug treatment recommendations and finding new drug targets for children diagnosed with a cancer of poor prognosis.
Telomere Length As A Biomarker In Paediatric Cancers
Funder
National Health and Medical Research Council
Funding Amount
$121,025.00
Summary
Telomeres are the ends of chromosomes, and their length is important to maintain cell viability. We intend to set up a reliable test to measure telomere length and also use this measurement in childhood cancer patients to assess whether patients with shorter telomeres are more susceptible to the adverse effects of chemotherapy and radiotherapy.
Improving Outcomes For Children With Cancer: Targeted Treatments And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$900,000.00
Summary
Child cancer is the commonest disease causing death in children. Relapse is due to small, treatment-resistant populations of cancer cells in the initial tumour. Improvements in cure rates have slowed due to poor investment by the pharmaceutical industry in targeting specific child cancer driver genes. My program of research will use novel technologies to identify: new vulnerabilities for combination drug therapies, drugs directed against child cancer gene targets and strategies for prevention.
Cancer Risks From Low-dose Ionising Radiation Following Diagnostic Medical Procedures
Funder
National Health and Medical Research Council
Funding Amount
$750,579.00
Summary
Our study investigates cancer risk following exposure to low doses of ionising radiation from medical procedures. Our first major paper linked over 800,000 CT exposures to cancer outcomes in a cohort of almost 11 million young Australians, and found that CT exposure predicted an increased incidence of leukaemia and most solid cancers. In our ongoing work we will incorporate nuclear medicine and other diagnostic x-rays, and estimate radiation dose for individual procedures and to specific organs.
Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a c ....Cancer is still a major cause of mortality in adults and children. Several lines of evidence suggest that some childhood cancers may arise due to factors, which interfere with the normal process of early development in embryonal tissues. The nature of the molecular factors which derail normal embryogenesis, their mechanism and timing, is vital information for efforts to generate novel pharmaceuticals. Moreover, factors which are necessary for tumour initiation, might be very good targets for a cancer prevention strategy. If entirely successful, our experiments will show that the MYCN oncoprotein is a key factor in the very earliest stages of neuroblastoma tumour formation, we will define the mechanism of the MYCN effect on the normal process of neural crest development, and, we will provide a basis for future cancer prevention strategies in children with this disease.Read moreRead less
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.
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.