The Role Of Microtubule Composition In The Efficacy Of Antimicrotubule Agents In Paediatric Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$173,380.00
Summary
To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggre ....To enhance the management of both childhood and adult cancers improved understanding of the processes responsible for tumour aggressiveness and drug resistance are required. Microtubules are important structural components of cells which are crucial for normal cell division. This makes microtubules excellent targets for anticancer drugs which can disrupt microtubules and kill cancer cells. This proposal will identify whether the microtubule composition of a tumour cell will predict for the aggressiveness of certain cancers, and whether this influences which tumours will respond to the vinca alkaloids. The vinca alkaloids are an important class of natural product drugs which disrupt microtubules and are particularly effective in the treatment of adult and childhood cancers. Unfortunately, some cancer cells fail to respond to this treatment due to the development of drug resistance. This proposal addresses vinca alkaloid resistance in children?s cancer and will determine why certain cancer cells fail treatment. Furthermore, this study will identify the role of certain components of microtubules that appear to be related to drug resistance in leukaemia and neuroblastoma cells and whose role is unknown. Chemotherapeutic drugs, such as the vinca alkaloids, are important in the treatment of cancer and knowledge about their interaction with their cellular target will improve the design of new drugs and treatment outcome.Read moreRead less
Transcriptional Regulation Of The Tumour Suppressor Gene, Retinoic Acid Receptor Beta
Funder
National Health and Medical Research Council
Funding Amount
$336,540.00
Summary
Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identif ....Cancer is still the second commonest cause of death in children. Neuroblastoma is the commonest solid tumour under the age of five years. Neuroblastoma responds poorly to conventional chemotherapy, unlike many other childhood cancers, and thus represents a major unsolved child health problem. A major advance in the field was a recent trial in th US demonstrating that treatment with oral vitamin A improved survival rates in children with advanced neuroblastoma. In previous studies we have identified that a particular gene retinoic acid receptor beta, known to be involved in the vitamin A anticancer effect may be deficient in some neuroblastoma tumours, and is vital to the anticancer effect of vitamin A in neuroblastoma cells. In this application we hope to define those cellular factors which are necessary for turning on the expression of this gene.Read moreRead less
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