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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.
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.
Optimising Targeted Polyamine Depletion For Treatment Of Childhood Neuroblastoma And Brain Tumours
Funder
National Health and Medical Research Council
Funding Amount
$928,152.00
Summary
Paediatric neuroblastoma and brain tumours, which often have dismal outcomes despite intensive therapy, have high levels of polyamines, which are essential for cell growth. We have shown that depleting polyamines, combined with chemotherapy, represents a highly promising therapy for neuroblastoma. We will make this exciting new treatment approach even more effective by comparing three ways of enhancing polyamine depletion, as a precursor to future neuroblastoma and brain tumour clinical trials.
EphA2 And EphA3 Maintain Tumour Initiating Cells And Are Therapeutic Targets In Brain Cancer
Funder
National Health and Medical Research Council
Funding Amount
$612,860.00
Summary
High-grade glioma (HGG) is the most common adult brain cancer; current treatments have increased survival times by months only. Our studies have shown brain cancer specific expression of a family of cell surface proteins called Eph receptors. Furthermore we have shown targeting these receptors with Eph antibodies leads to a significant reduction in brain cancer tumour growth. We now propose to test targeting these receptors in combination to achieve greater responses with minimal side effects.
Immunotherapy has recently shown promise in bone cancer. We have found that while immune modulators Il-6 and Ifn?? contribute to tumour suppression Il-23 promotes the growth of radiation-induced bone cancer. We have generated mouse models of bone cancer to investigate tumour growth and immune surveillance in immune competent mice with an overall aim of identifying therapeutic targets in this disease.
Characterisation Of Two Novel Markers Of Osteosarcoma Metastasis As Potential Therapeutic Targets
Funder
National Health and Medical Research Council
Funding Amount
$624,500.00
Summary
Osteosarcoma (OS) is the most common bone tumour in children and adolescents. In spite of aggressive chemotherapy, OS tumours that metastasise to the lungs result in dismal long-term survivals of only 10-20%. For these patients, new treatment options are desperately needed. In this proposal we show compelling data identifying two new markers of OS metastasis. This research aims to validate the suitability of these novel markers as therapeutic targets to prevent OS metastasis.
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.
Control Of Gastrointestinal Tumour Progression By Therapeutic Interference With Myeloid Derived Cells
Funder
National Health and Medical Research Council
Funding Amount
$758,678.00
Summary
Cancers of the stomach and the colon are a major health burden. Despite our increased molecular understanding of the mutation that cause these cancers our treatment options are very limited. Here we will use sophisticated and validated mouse models for these cancers to establish how blood-borne cells contribute to the growth and spreading of these cancer. We will use these models to establish highly effective treatment combinations of therapeutic agents that are already undergoing preclinical te ....Cancers of the stomach and the colon are a major health burden. Despite our increased molecular understanding of the mutation that cause these cancers our treatment options are very limited. Here we will use sophisticated and validated mouse models for these cancers to establish how blood-borne cells contribute to the growth and spreading of these cancer. We will use these models to establish highly effective treatment combinations of therapeutic agents that are already undergoing preclinical testing.Read moreRead less
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.
Colorectal cancer (CRC) is one of the most common causes of cancer-associated death in the world. We aim to understand why some CRC patients stop responding to EGFR therapy. In particular, we will study small molecules called cytokines that are produced by the tumour microenvironment and determine if the inhibition of these cytokines can over-come the acquired resistance to therapy. Our goal is to identify new ways to improve the current treatment options for CRC patients.