The role of microtubule composition in the efficacy of antimicrotubule agents in paediatric malignancy

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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.