Multidrug Resistance Mediated by P-glycoprotein

P-糖蛋白介导的多药耐药性

基本信息

批准号：
8350051
负责人：
Antonio Fojo
金额：
$ 46.93万
依托单位：
DIVISION OF CLINICAL SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
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/8350051
关键词：
ABCB1 gene ABCG2 gene Accounting Adrenal Gland Neoplasms Adult Affect Area Biology Brain Bypass Child Clinical Complex Cytotoxic agent DNA Sequence Rearrangement Development Drug resistance Educational process of instructing Etiology Evaluation Frequencies Gastrointestinal tract structure Gene Rearrangement Genes Genetic Goals Homologous Gene Human Human Biology Impairment In Vitro Investigation Knock-out Knockout Mice Knowledge Lead Learning Lymphoma Mediating Modeling Molecular Multi-Drug Resistance Mus Nervous system structure Neurons Normal tissue morphology Oral Outcome P-Glycoprotein Patients Pharmaceutical Preparations Physiological Refractory Refractory Disease Research Resistance Role Sampling Toxic effect Transcript Wild Type Mouse Work base chemobrain chemotherapeutic agent chemotherapy design effective therapy experience in vivo interest malignant breast neoplasm novel novel strategies prevent research study resistance mechanism response tumor tumor growth

项目摘要

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.

我们的研究目标是（1）了解获得性耐药性的分子基础（2）理解这些变化如何/为何发生； (3) 在临床样本中寻找它们，(4) 制定策略来减少或预防它们的发生。我们的努力越来越多地致力于了解正常组织如何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 ABCG2）保护的程度。我们也一直在研究药物转运蛋白的作用药物转运蛋白提供大脑免受化疗药物的保护。部分原因是我们认识到，随着我们开发出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，因为许多相同的转运蛋白保护大脑沿着胃肠道排列，如果要口服给药，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可能产生的后果。