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Core B: Preclinical Therapeutics Core

核心 B：临床前治疗核心

基本信息

批准号：
9904488
负责人：
Cyril Henri Benes
金额：
$ 23.21万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9904488
关键词：
3-Dimensional Allografting Autophagocytosis Biological Assay Biological Markers Biological Models Biology Cancer Center Cell Culture Techniques Cell Line Cell Survival Cells Clinical Trials Collection Computer Models Correlative Study Data Data Analyses Drug Combinations Drug Screening Drug Targeting Epigenetic Process Evaluation Gene Expression General Hospitals Genetic Genetic Models Genetically Engineered Mouse Growth Histopathology Hospitals Human Image Immune Immune system Immunocompetent Immunomodulators In Vitro Infrastructure Investigation KRAS2 gene Libraries Liquid substance Malignant Neoplasms Malignant neoplasm of pancreas Massachusetts Measurement Metabolic Metabolic Pathway Metabolism Modeling Molecular Mus Nutrient Pancreatic Ductal Adenocarcinoma Pathology Pathway interactions Patients Pharmaceutical Preparations Pharmacology Pre-Clinical Model Preclinical Drug Evaluation Predisposition Regulation Research Personnel Series Signal Pathway Subgroup Technology Testing Therapeutic Therapeutic Agents Treatment Efficacy Validation base cancer therapy candidate marker clinical application clinical translation clinically relevant comparative cytokine design drug sensitivity drug use screening efficacy study exome sequencing high throughput screening high-throughput drug screening in vivo in vivo Model inhibitor/antagonist innovation insight novel novel therapeutic intervention nutrient deprivation pre-clinical screening small molecule targeted treatment therapeutic candidate therapeutic evaluation tool tumor virtual

项目摘要

Summary – Core B (Preclinical Therapeutics) The Preclinical Therapeutics Core will leverage the expertise and infrastructure of the Center for Molecular Therapeutics at the Massachusetts General Hospital and of the Center for Co-Clinical Trials at the MD Anderson Cancer Center. High throughput drug screening of established and project derived cells representing the array of PDAC subtypes will be performed. A curated collection of clinically relevant compounds as well as novel compounds specifically relevant to the projects will be used in 2D and 3D cell viability assays using defined metabolic conditions. Signaling pathway and immune-modulator measurements will also be performed to inform mechanism of action and evaluate the impact of treatments on the interaction between PDAC cells and the immune system. Data that emerge from in vitro screens will be prioritized for in vivo efficacy studies at the Center for Co-Clinical Trials. Here, a dedicated pharmacology staff will evaluate single agents or drug combinations in the most relevant pre-clinical PDAC models, including human PDx and autochthonous GEM models. Through comprehensive pharmacologic analyses, the Core B aims to evaluate novel therapeutic approaches and define biomarkers that may predict responsiveness in clinical trials.

总结-核心B（临床前治疗）临床前治疗核心将利用分子生物学中心的专业知识和基础设施，马萨诸塞州总医院和MD联合临床试验中心的治疗药物安德森癌症中心。已建立和项目衍生细胞的高通量药物筛选将执行表示PDAC子类型的阵列的操作。一个精选的临床相关的化合物以及与项目特别相关的新型化合物将用于2D和3D细胞使用确定的代谢条件进行活力测定。信号通路和免疫调节剂测量还将进行，以告知作用机制并评价治疗对相互作用的影响 PDAC细胞和免疫系统之间的联系从体外筛选中获得的数据将优先用于协同临床试验中心的体内疗效研究。在这里，一个专门的药理学工作人员将评估最相关的临床前PDAC模型中的单药或药物组合，包括人PDx和本土GEM模型。通过全面的药理学分析，核心B旨在评估新的治疗方法，并确定生物标志物，可以预测在临床试验中的反应。