RAD001 THERAPY OF ANGIOMYOLIPOMATA IN PATIENTS WITH TSC

RAD001 血管平滑肌脂肪瘤治疗 TSC 患者

• 批准号: 7374557
• 负责人: JOHN J BISSLER
• 金额: $ 0.53万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7374557
• 关键词: RAD001; THERAPY; ANGIOMYOLIPOMATA; PATIENTS; TSC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Targeted molecular therapy is the ultimate objective for the management of malignancy, but only a few examples exist, due in large part to the complexity of genetic events that result in unregulated cell growth. Tuberous sclerosis is an inherited cancer syndrome associated with the formation of hamartomas in multiple organs, including angiomyolipomas in the kidney, caused by well-characterized inactivating mutations at genetic loci that encode the interacting proteins, tuberin or hamartin. Recent studies have elucidated the pivotal role of the tuberin/hamartin complex in controlling the Akt signaling pathway that regulates cell growth and division. The objective of this study is to determine if an mTOR inhibitor reduces the volume of angiomyolipomas. This goal will be accomplished by treatment of thirty patients with angiomyolipomas, either in the setting of tuberous sclerosis, or a related disease associated with mutations in tuberous sclerosis genes called sporadic lymphangioleiomyomatosis, with dose-adjusted RAD001 for a period of one year. The size, number, volume and tissue composition of renal angiomyolipomas will be monitored by MRI or CT scans of the kidney, performed prior to treatment, at six months, one and two years. The dose of RAD 001 will be modified to see if there is a threshold does that leads to apoptosis versus a mere cell volume change.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。靶向分子治疗是治疗恶性肿瘤的最终目标，但只有少数例子存在，这在很大程度上是由于导致细胞生长失控的遗传事件的复杂性。结节性硬化症是一种遗传性癌症综合征，与多个器官中错构瘤的形成相关，包括肾脏中的血管平滑肌脂肪瘤，这是由编码相互作用蛋白、马铃薯蛋白或错构蛋白的基​​因位点的明确失活突变引起的。最近的研究阐明了马铃薯球蛋白/错构瘤蛋白复合物在控制调节细胞生长和分裂的 Akt 信号通路中的关键作用。本研究的目的是确定 mTOR 抑制剂是否可以减少血管平滑肌脂肪瘤的体积。这一目标将通过使用剂量调整的 RAD001 治疗 30 名血管平滑肌脂肪瘤患者来实现，这些患者要么患有结节性硬化症，要么患有与结节性硬化症基因突变相关的疾病（称为散发性淋巴管平滑肌瘤病）。肾血管平滑肌脂肪瘤的大小、数量、体积和组织成分将通过在治疗前、六个月、一年和两年时进行的肾脏 MRI 或 CT 扫描来监测。将修改 RAD 001 的剂量，看看是否存在导致细胞凋亡与单纯细胞体积变化的阈值。