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.

项目摘要 该中心的科学前提是乳腺癌患者衍生的Xenographotic（PDX）模型 代表人类乳腺肿瘤的多样性，可用于测试新药和药物 合并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 促进在国家癌症研究所在乳腺癌临床试验中测试的药物的优先级 （NCI）。为了实现这一目标，我们的PDTC专注于测试已通过NCI可用的药物 作为具有实验治疗临床试验网络（ETCTN）的NCI-IND代理。从科学上讲 该PDTC将重点介绍批准和研究药物和药物的临床前评估 代表原发性乳房和转移性乳房的大量乳腺PDX模型的组合 癌症。一个项目将筛选35种NCI-IND药物为单一药物，并结合标准药物 护理疗法，使用新的类器官系统中的> 100个乳腺PDX模型，并验证这些模型 含PDX的小鼠的反应。另一个项目将测试预测靶向肿瘤的疗法 启动细胞群体，目的是降低化学疗法的耐药性和复发性 - 主要 乳腺癌死亡原因。这两个协同研究项目将得到支持 关键核心：PDX核心传播PDX模型并运行药物研究；生物统计学和 生物信息学核心识别肿瘤的分子特征（或不反应） 治疗；飞行员项目和跨网络活动的核心，以促进探索新想法 PDTC并与PDXNETWORK（PDXNET）合作；以及一个促进的行政核心 PDTC和PDXNET内的有效沟通。两者一起，这些要素将 收敛以揭示乳腺癌患者未来临床试验的高优先级治疗策略。