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衍生的异种移植(PDX)模型 代表了人类乳腺肿瘤的多样性，可以可行地用于测试新药和药物 寻找与不同肿瘤类型的分子特征相匹配的治疗方法。 我们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要测试的药物的优先顺序 (NCI)。为了实现这一目标，我们的PDTC专注于测试已通过NCI获得的药物 作为NCI-IND药物与实验治疗临床试验网络(ETCTN)合作。从科学上讲， 这个PDTC将专注于已批准和研究的药物和药物的临床前评估 代表原发和转移性乳腺的大量乳腺PDX模型的组合 癌症。一个项目将筛选35种NCI-IND药物作为单一药物，并与标准药物相结合- 护理疗法，在&gt；100个乳房PDX模型中使用新的有机系统，并验证这些 对携带PDX的小鼠的反应。另一个项目将测试预计将针对肿瘤的治疗方法- 启动细胞群体，目标是减少化疗耐药性和复发-主要 乳腺癌的死因。这两个协同研究项目将得到几个 关键核心：用于传播PDX模型和运行药物研究的PDX核心；生物统计和 生物信息学核心，用于识别对各种疾病有反应(或无反应)的肿瘤的分子特征 治疗；试点项目和跨网络活动核心，以促进对新想法的探索 PDTC并与PDXNetwork(PDXNet)合作；以及一个行政核心，以促进 在PDTC内部和与PDXNet的有效沟通。综合起来，这些元素将 汇聚以揭示未来乳腺癌患者临床试验的高优先级治疗策略。

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.