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.
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.
In melanoma we hypothesise there is a series of as yet unidentified gene fusions which provide oncogenic stimulatory signals that promote tumour growth and that these novel fusion products are excellent targets for the design of new therapies to treat melanoma. The aims of this study are to identify oncogenic fusions in melanoma, to assess which of these are recurrent, and to demonstrate that the resulting fusion proteins provide a selective growth and-or survival advantage to the tumour cell.
A number of previous studies have shown high levels of two proteins, STC1 and STC2, in a substantial subset of breast cancers. We are proposing to do the first definitive analyses of whether these hormone-like proteins contribute to breast cancer growth. If yes, they are suitable targets for development of new treatments.
Control Of The Ras/Erk Signaling Pathway By The Brahma Chromatin-remodeling Complex
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Hormones bind and initiate molecular signals within cells to proliferate or change into specific cell types. This is important for growth and development of different tissues. A pathway which is critical for transmitting the effects of hormones in cells is the Ras pathway. New studies by the applicants indicate that the Brahma complex, a molecule important in controlling the levels of proteins in cells, activates the Ras pathway. This project will define how Brahma controls the Ras pathway.
Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.