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

为了加强对儿童和成人癌症的管理，需要更好地了解肿瘤侵袭性和耐药性的过程。微管是细胞的重要结构成分，对于细胞正常分裂至关重要。这使得微管成为抗癌药物的极好靶点，抗癌药物可以破坏微管并杀死癌细胞。这项提案将确定肿瘤细胞的微管组成是否会预测某些癌症的侵袭性，以及这是否会影响哪些肿瘤对长春花生物碱产生反应。长春花生物碱是一类重要的天然产物药物，其破坏微管并且在成人和儿童癌症的治疗中特别有效。不幸的是，由于耐药性的发展，一些癌细胞对这种治疗没有反应。这项提案解决了儿童对长春花生物碱的耐药性？它将决定为什么某些癌细胞治疗失败。此外，这项研究将确定微管的某些成分的作用，这些成分似乎与白血病和神经母细胞瘤细胞的耐药性有关，其作用尚不清楚。化学药物，如长春花生物碱，在癌症治疗中很重要，了解它们与细胞靶点的相互作用将改善新药的设计和治疗效果。

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.