Use of retroviral expression libraries to characterise mechanisms of drug resistance in leukaemia.

目前，白血病的治疗要么基于已确立的化疗药物治疗，要么基于目前作为临床试验的一部分正在测试的新鉴定的抑制剂药物。已知这两种治疗在某些情况下会诱导或选择对药物的耐药性。耐药性通常会降低使用相同或类似药物进行进一步治疗的成功率。为了发现克服耐药性的可能方法，重要的是要了解负责的机制。迄今为止，已知许多导致耐药性的机制，但仍存在与耐药性相关的未鉴定的机制。我们工作的目的是使用一种新的方法来确定白血病中未知的耐药机制。一旦确定了一种机制，我们将通过筛选一些对治疗表现出耐药性的患者来确定其在白血病中的相关性。如果确定为白血病患者的常见耐药机制，我们将测试可能的药物，能够防止耐药性，可以在治疗过程中与药物联合使用，并筛选新的药物对耐药机制的敏感性。在治疗前检测已知耐药机制的诊断试验可用于为个体患者选择最合适的药物组合。一些已知的耐药机制发生在白血病中，也适用于其他形式的癌症，该项目与癌症化疗普遍相关。

At present, treatment of leukaemia is based either on established chemotherapeutic drug treatment or newly identified inhibitor drugs currently being tested as part of clinical trials. Both these treatments are known to induce or select for resistance to the drugs in some cases. Resistance usually reduces the success rate of any further treatment with the same or similar drugs. To discover possible ways of overcoming drug resistance it is important to understand the mechanisms that are responsible. To date a number of mechanisms that cause resistance are known, but there are still unidentified mechanisms that are associated with drug resistance. The aim of our work is to use a new method to identify unknown drug resistance mechanisms in leukaemia. Once a mechanism is identified, we will determine its relevance in leukaemia by screening a number of patients that have shown resistance to treatment. If identified as a common mechanism of resistance in leukaemic patients, we will test possible agents able to prevent drug resistance that could be used in conjunction with drug during treatment, and to screen new drugs for susceptibility to resistance mechanisms. Diagnostic tests to detect the presence of the known resistance mechanisms prior to treatment could be used in selection of the most appropriate drug combinations for individual patients. Some of the known drug resistance mechanisms that occur in leukaemia are also operative in other forms of cancer and the project is of general relevance to cancer chemotherapy.