OF WILMS TUMOR XENOGRAFTS U S Food 肾母细胞瘤裸鼠移植瘤的灵敏度的美国食品ppt课件.ppt

美国自发性脑出血处理指南课件慢性鼻炎吃什么药好慢性鼻窦炎吃什中医中药治疗高血脂饮食保健资料子宫肌瘤合并胆囊炎围手术期护理中医药对冠心病稳定性心绞痛长期治疗价值 慢性单纯性苔藓痤疮白癜风教材课程 Predictive Models of CancerXenograft Models Of Childhood Solid Tumors Solid Malignancies Group St. Jude Children’s Research Hospital Drug Development For Children Has To Be Different Drug acquired NCI/Industry/Academia Phase I Unacceptable Toxicity Active Inactive Phase III Virtually no drugs are developed specifically to treat childhood solid tumors. Aim: Develop and validate tumor models to identify potentially important new drugs. Phase II Discard Discard Does phase II testing reveal any insight as to why this drug succeeds or fails? Aim: Develop predictive models. How do phase I trials help to prioritize drugs for phase II evaluation? Aim:Develop a process allowing more rational prioritization. Human Tumor Xenografts Human cancers grown in immune-incompetent mice/rats. Models of most childhood solid tumors. Models of childhood ALL established. Xenograft Model Validation(Rhabdomyosarcoma) Model tumors respond qualitatively and quantitatively to drugs known to be active in the respective clinical disease: Diagnosis models: highly sensitive. Relapse models: significantly less responsive Models prospectively identify effective agents. √ √ √ Retrospective and Prospective Use of Rhabdomyosarcoma Xenografts SENSITIVITY OF WILMS TUMOR XENOGRAFTS Entering into a collaboration with GSK who identified a potential Wilms target through a genomics/proteomics screen Where do Xenograft Models Fit? Drug acquired NCI/Industry/Academia Phase I Identification of novel agents Mechanisms- molecular targets Broad spectrum activity Lack of cross-resistance Optimizing schedules of administration Developing relationships between response and systemic exposures Phase II Optimizing schedules of administration Schedule-Dependency of Camptothecins that Target Topoisomerase I Importance of SchedulingEmerging Clinical Data Topotecan Response Rate Solid Tumors Schedule Sample Size Inve