Multidrug Resistance Mediated by P-glycoprotein

P-糖蛋白介导的多药耐药性

• 批准号: 8158266
• 负责人: Antonio Fojo
• 金额: $ 44.65万
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8158266
• 关键词: Mediating; Multi-Drug Resistance; P-Glycoprotein; P-Glycoproteins

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.

我们的研究目标是（1）了解获得性耐药的分子基础（2）理解这些变化如何/为什么发生;（3）在临床样本中寻找它们;（4）制定减少或预防它们发生的策略。我们的努力越来越多地针对了解正常组织可能受到这些药物的影响，以及它们可能或可能不受药物转运蛋白（如P-糖蛋白和半转运蛋白ABCG 2）保护的程度。我们还一直在研究药物转运蛋白在提供脑保护免受化疗药物影响方面的作用。部分原因是我们认识到，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，并赋予其作为避难所的地位，因为许多保护胃肠道的相同转运蛋白，如果要口服药物，药物必须设计成绕过它们。我们正在进行研究，希望了解保护大脑的机制，以及绕过这些障碍的后果。我们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实现这一目标，目的是进一步了解这个问题。