PDX Trial Center for Breast Cancer Therapy

项目摘要 该中心的科学前提是，乳腺癌患者来源的异种移植物（PDX）模型 代表了人类乳腺肿瘤的多样性，并可切实用于测试新药和药物 组合以找到与各种肿瘤类型的分子特征相匹配的治疗方法。 我们的PDX开发和试验中心（PDTC）的目标是获得临床前数据， 促进国家癌症研究所乳腺癌临床试验中测试药物的优先顺序 （NCI）。为了实现这一目标，我们的PDTC专注于测试已经通过NCI提供的药物 作为NCI-IND药物与实验治疗药物临床试验网络（ETCTN）合作。科学家， 该PDTC将重点关注已批准和研究药物的临床前评价， 在代表原发性和转移性乳腺癌的大量乳腺PDX模型中， 癌一个项目将筛选35种NCI-IND药物作为单药，并与标准药物联合使用， 在>100个使用新型类器官系统的乳腺PDX模型中进行护理治疗，并验证这些 在携带PDX的小鼠中的反应。另一个项目将测试预计针对肿瘤的疗法- 启动细胞群，以减少化疗耐药性和复发为目标-主要 乳腺癌的死亡原因。这两个协同研究项目将得到几个 关键核心：PDX核心，用于传播PDX模型并运行药物研究;生物统计学和 生物信息学核心，以确定肿瘤的分子特征，这些特征对各种 治疗;试点项目和跨网络活动核心，以促进探索新的想法 PDTC并与PDXNetwork（PDXNet）合作;以及一个行政核心，以促进 PDTC内部以及与PDXNet的有效沟通。综合起来，这些要素将 汇集揭示高优先级的治疗策略，为未来的临床试验在乳腺癌患者。

Project Summary The scientific premise of this Center is that breast cancer patient-derived xenograft (PDX) models represent the diversity of human breast tumors, and can be feasibly utilized to test new drugs and drug combinations to find therapeutic approaches that match with molecular features of various tumor types. The goal of our PDX Development and Trials Center (PDTC) is to obtain preclinical data that will facilitate prioritization of drugs to be tested in breast cancer clinical trials at the National Cancer Institute (NCI). Toward this goal, our PDTC focuses on testing drugs that are already available through the NCI as NCI-IND agents with the Experimental Therapeutics Clinical Trials Network (ETCTN). Scientifically, this PDTC will focus on preclinical evaluation of approved and investigational drugs and drug combinations in a large collection of breast PDX models representing primary and metastatic breast cancer. One project will screen 35 NCI-IND drugs as single agents and in combination with standard- of-care therapies, in >100 breast PDX models using a novel organoid system, and validate these responses in PDX-bearing mice. Another project will test therapies that are predicted to target tumor- initiating cell populations, with the goal of reducing chemotherapy resistance and recurrence – the major cause of death from breast cancer. These two synergistic research projects will be supported several key Cores: a PDX Core to propagate the PDX models and run the drug studies; a Biostatistics and Bioinformatics Core to identify molecular features of tumors that do (or do not) respond to various treatments; a Pilot Projects and Trans-network Activities Core to foster exploration of new ideas within the PDTC and in collaboration with the PDXNetwork (PDXNet); and an Administrative Core to facilitate effective communication within the PDTC and with the PDXNet. Taken together, these elements will converge to reveal high-priority treatment strategies for future clinical trials in breast cancer patients.