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）和类器官模型 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 PDTC专注于为乳腺癌确定新的治疗策略，乳腺癌仍然是第二大原因 女性癌症死亡率。我们将在模型中进行药物和药物组合的临床前评价 从我们大量收集的261个乳腺PDX模型和>100个代表原发性的稳定PDxO系中选择， 来自不同患者人群的转移性和耐药乳腺癌（25%的收集来自 少数种族/族裔，并计划在两个研究项目的目标1中增加这一比例）。中心 包括两个高度综合的研究项目，旨在共同打击两个最困难的 导致乳腺癌死亡的问题：乳腺癌复发和复发/转移性乳腺癌的治疗 疾病超过90%的乳腺癌死亡归因于疾病复发，即无法治愈的转移性疾病。 项目1的重点是改善早期三阴性乳腺癌（TNBC）的治疗， 通过确定最佳化疗和靶向治疗组合， 基于肿瘤的分子特征。项目2旨在确定更有效的治疗方案， 复发（耐药，转移性疾病），通过利用我们独特的PDX和PDxO集合， 转移性样本这两个互补的研究项目将得到PDX核心的支持， 生物信息学核心，一个试点项目和跨网络活动核心，促进新思想的探索 在PDTC内并与PDXNetwork（PDXNet）合作，以及一个管理核心， 项目监督和管理，并促进PDTC和PDXNet内部的有效沟通。 PDX开发和试验中心（PDTC）的首要目标是获得临床前数据， 促进国家癌症研究所（NCI）乳腺癌临床试验中测试药物的优先级。

Project Summary The scientific premise of this Center is that breast cancer patient-derived xenograft (PDX) and organoid 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. Our PDTC is focused on identifying new treatment strategies for breast cancer, which remains the 2nd leading cause of cancer death in women. We will conduct preclinical evaluation of drugs and drug combinations in models selected from our large collection of 261 breast PDX models and >100 stable PDxO lines representing primary, metastatic, and treatment-resistant breast cancers from diverse patient populations (25% of the collection is from racial/ethnic minorities, with plans to increase that proportion in Aim 1 of both research projects). The Center comprises two highly integrated Research Projects that are designed together to combat the two most difficult problems contributing to breast cancer deaths: breast cancer recurrence, and treatment of recurrent/metastatic disease. More than 90% of breast cancer deaths are attributed to disease recurrence as incurable metastatic disease. Project 1 is focused on improving therapy for early-stage triple negative breast cancer (TNBC), to prevent recurrence and achieve durable cures by identifying optimal chemotherapy and targeted therapy combinations based on molecular features of tumors. Project 2 aims to identify more effective regimens in disease that does recur (treatment-resistant, metastatic disease) by utilizing our unique collection of PDX and PDxO from metastatic samples. These two complementary research projects will be supported by a PDX Core, a Bioinformatics Core, a Pilot Projects and Trans-Network Activities Core that fosters exploration of new ideas within the PDTC and in collaboration with the PDXNetwork (PDXNet), and an Administrative Core that provides project oversight and management, and facilitates effective communication within the PDTC and the PDXNet. The overarching 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).