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建立的化疗药物治疗，要么基于新发现的抑制剂药物，目前正在作为临床试验的一部分进行测试。已知这两种治疗方法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，了解产生耐药性的机制是很重要的。迄今为止，许多引起耐药性的机制是已知的，但与耐药性有关的机制仍未确定。我们工作的目的是使用一种新的方法来识别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有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一种常见耐药机制，我们将测试能够预防耐药的可能药物，这些药物可在治疗期间与药物联合使用，并筛选新药对耐药机制的易感性。在治疗前检测已知耐药机制是否存在的诊断试验可用于为个别患者选择最适当的药物组合。白血病中出现的一些已知耐药机制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.