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资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。靶向分子治疗是恶性肿瘤管理的最终目标，但仅存在少数实例，这在很大程度上是由于导致不受调节的细胞生长的遗传事件的复杂性。硬化症是一种遗传性癌症综合征，与多器官错构瘤（包括肾脏血管平滑肌脂肪瘤）的形成相关，由编码相互作用蛋白质（块茎蛋白或错构蛋白）的遗传基因座的充分表征的失活突变引起。最近的研究已经阐明了tuberin/hamartin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抑制剂是否能减少血管平滑肌脂肪瘤的体积。这一目标将通过30例血管平滑肌脂肪瘤患者的治疗来实现，无论是在结节性硬化症的背景下，还是与结节性硬化症基因突变相关的称为散发性淋巴管平滑肌瘤病的相关疾病中，使用剂量调整的RAD 001治疗一年。将在治疗前、6个月、1年和2年时通过肾脏MRI或CT扫描监测肾血管平滑肌脂肪瘤的大小、数量、体积和组织组成。将修改RAD 001的剂量，以查看是否存在导致细胞凋亡的阈值，而不是仅仅细胞体积变化。