Multidrug Resistance Mediated by P-glycoprotein

我们的研究目标是(1)了解获得性耐药的分子基础；(2)了解这些变化是如何/为什么发生的；(3)在临床样本中寻找它们；(4)设计减少或防止它们发生的策略。我们的努力越来越多地针对了解这些药物如何影响正常组织以及它们可能在多大程度上受到药物转运体的保护，如P-糖蛋白和半转运体ABCG2。我们还一直在研究药物转运体在提供对化疗药物的大脑保护方面的作用。部分原因是认识到，随着我们开发越来越多的口服药物，我们正在开发的药物可能会绕过保护大脑的机制，并赋予其避难所的地位，因为许多保护胃肠道的转运体排列在一起，如果要口服的话，药物必须被设计成绕过它们。我们正在进行研究，希望了解保护大脑的机制，以及绕过这些障碍可能产生的后果。我们正在通过检查体外和体内模型以及对现有临床数据的详尽搜索来做到这一点，目的是进一步了解这个问题。

Our research goals have been to (1) understand the molecular basis of acquired drug resistance (2) comprehend how/why these changes occur; (3) search for them in clinical samples and (4) devise strategies to reduce or prevent their occurrence. Our efforts are increasingly directed at understanding how normal tissue might be affected by these agents and the extent to which they might or might not be protected by drug transporters such as P-glycoprotein and the half-transporter, ABCG2 We have also been investigating the role of drug transporters in affording the brain protection from chemotherapeutic agents. Driven in part by the recognition that as we develop more and more agents to be administered orally, we are developing agents that are likely to bypass the mechanisms that protect the brain and confer its status as a sanctuary, since many of the same transporters that protect line the GI tract, and drugs must be designed to bypass them if they are to be administered orally. We are conducting studies to hopefully understand the mechanisms that protect the brain and what might be the consequences of bypassing these barriers. We are doing this by both examining in vitro and in vivo models and through an exhaustive search of existing clinical data with the goal of further understanding this problem.