PDX Trial Center for Breast Cancer Therapy

PDX 乳腺癌治疗试验中心

• 批准号: 9446429
• 负责人: Michael T. Lewis
• 金额: $ 248.22万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9446429
• 关键词: Animals; Bioinformatics; Biometry; Breast; Breast Cancer Patient; Breast Cancer therapy; Cancer Biology; Cancer Etiology; Carboplatin; Cause of Death; Cells; Cellular biology; Cessation of life; Clinical; Clinical Trials; Collaborations; Collection; Communication; Comprehensive Cancer Center; Data; Development; Diagnosis; Disease; Drug Combinations; Drug Evaluation; Drug Targeting; Elements; Environment; FDA approved; Fostering; Funding; Future; Generations; Genomics; Goals; Grant; Human; Institutes; Investigational Drugs; Investigational Therapies; Laboratories; Malignant Neoplasms; Mammary Neoplasms; Medical Oncology; Medicine; Metastatic breast cancer; Molecular; Molecular Genetics; Mus; National Cancer Institute; Organoids; Pathology; Patient-derived xenograft models of breast cancer; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Population; Preclinical Drug Evaluation; Recurrence; Reproducibility; Research; Research Personnel; Research Project Grants; Resistance; Resources; Running; Site; Structure; System; Testing; Therapeutic; Therapeutic Clinical Trial; Translational Research; Tumor Initiators; Woman; Work; Xenograft Model; Xenograft procedure; anticancer research; base; cancer clinical trial; chemotherapy; clinical investigation; cohort; college; drug testing; experience; in vivo; industry partner; malignant breast neoplasm; member; multidisciplinary; novel; novel drug combination; novel therapeutic intervention; novel therapeutics; oncology; pre-clinical; precision medicine; preclinical evaluation; preclinical trial; response; standard of care; therapeutic evaluation; treatment strategy; tumor

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.

项目概要 该中心的科学前提是乳腺癌患者来源的异种移植（PDX）模型 代表了人类乳腺肿瘤的多样性，可用于新药和新药的测试 组合来寻找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，以便 促进国家癌症研究所乳腺癌临床试验中待测药物的优先顺序 （国家癌症研究所）。为了实现这一目标，我们的 PDTC 重点测试已通过 NCI 提供的药物 作为实验治疗临床试验网络 (ETCTN) 的 NCI-IND 药物。从科学角度来说， 本次 PDTC 将重点关注已批准和研究药物以及药物的临床前评估 代表原发性和转移性乳腺的大量乳腺 PDX 模型中的组合 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组合 使用新型类器官系统在超过 100 个乳腺 PDX 模型中进行非护理疗法，并验证这些 携带 PDX 的小鼠的反应。另一个项目将测试预计针对肿瘤的疗法 启动细胞群，目标是减少化疗耐药性和复发——主要 乳腺癌死亡原因。这两个协同研究项目将得到多项支持 关键核心：用于传播 PDX 模型并运行药物研究的 PDX 核心； a 生物统计学和 生物信息学核心，用于识别对各种因素有反应（或没有反应）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；和一个行政核心，以促进 PDTC 内部以及与 PDXNet 的有效沟通。综合起来，这些要素将 汇聚揭示乳腺癌患者未来临床试验的高度优先治疗策略。