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Preclinical Models and Therapeutics Core

临床前模型和治疗核心

基本信息

批准号：
9788316
负责人：
Giorgio Inghirami
金额：
$ 11.68万
依托单位：
MAYO CLINIC ARIZONA
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/9788316
关键词：
3-Dimensional Animals Applications Grants Automobile Driving Bioinformatics Biological Assay Biology Biometry Cancer Biology Cancer Model Cancer Patient Cell Line Clinical Clinical Research Collaborations Complex Cryopreservation Cryopreserved Tissue Data Data Analyses Defect Development Dissection Drug Screening Drug resistance EGFR gene End Point Assay Engineering Evaluation Fingerprint Fostering Funding Generations Genetic Genomics Hematological Disease Hematology Heterogeneity Human Immunocompromised Host In Vitro Intervention Investigational Drugs Knowledge Lesion Libraries Lymphoma Malignant Neoplasms Mature T-Lymphocyte Mission Modality Modeling Molecular Molecular Diagnosis Molecular Profiling Mus Neoplasms Organ Organoids Pathologic Patients Pharmaceutical Preparations Phenotype Pre-Clinical Model Preclinical Testing Preparation Primary Lesion Procedures Property Public Health Reagent Reproducibility Research Research Personnel Role Sampling Solid Standardization Stratification T-Cell Lymphoma T-Cell and NK-Cell Neoplasm Testing Therapeutic Tissue Sample Transgenic Organisms Treatment Protocols Tumor-Derived Validation Work Xenograft Model Xenograft procedure base biobank cancer therapy cancer type data mining data warehouse design efficacy evaluation established cell line functional genomics improved in vitro Model in vitro activity in vivo individual response innovation large cell Diffuse non-Hodgkin&apos s lymphoma medical schools member mouse model novel novel therapeutic intervention outcome forecast pre-clinical preclinical evaluation preclinical trial predictive modeling programs response success targeted treatment therapeutic target three dimensional cell culture tissue resource transcriptome sequencing translational cancer research treatment response tumor tumor heterogeneity tumor xenograft

项目摘要

Contact PD/PI: Rimsza, Lisa Shared-Res-Core-003 (458) The Preclinical Models and Therapeutics Core (PMTC) will generate/assemble and characterize a wide array of patient derived tumor xenograft (PDTX) models and patient derived organoids (PDO). We will use PDTX models to conduct in vivo preclinical animal studies described in Projects 1, 2, 3 and 4. This will allow for efficient and consistent evaluation of the efficacy of the novel therapeutic approaches proposed in each of the Projects. Translational cancer research has been greatly facilitated by the demonstration that human tumors can be grown as xenografts in immunocompromised mice, and the use of PDTX has significantly increased the public knowledge of cancer biology and improved the preclinical evaluation and predictability of investigational drugs. Historically, as high as 85% of drugs with in vitro activity have failed in human studies. More importantly, PDTX were proven to maintain many of the features of the original patient tumors, including expression phenotypes, genomic landscape and tumor heterogeneity and intrinsic properties such as their ability to colonized/disseminate into specific organs. This allows for the design and implementation of highly informative pre-clinical trials, capable of anticipating the responses of individual cancer patients. PDTX serve as a renewable, quality-controlled tissue resource for preclinical evaluation of novel treatment regimens and will be the principal platform for evaluation of the efficacy of the targeted therapies, outlined in the Projects of this current application. Although many PDTX have been established from solid cancers, PDTX from hematological disorders are still rare and no comprehensive libraries exist. Here we will focus on the generation and characterization of PDTX from DLBCL and T-cell lymphoma, which remains an unmet clinical need. It is now recognized that the poor therapeutic success in this arena is largely due to the complex heterogeneity of these neoplasms, as well as, in the case of mature T-cell neoplasms, the lack of “bona fide” cell lines or reproducible and informative mouse models. Both PDTX and derived 2D/3D in vitro models will be molecularly profiled (WES/target sequencing, total RNA-Seq and ERBBS) and validated using functional approaches. Preclinical testing will be available using a battery of conventional and novel compounds. PDTX are particularly useful for in vivo mechanistic studies through the use of PDOs, and the information from these studies will be instrumental in understanding the biology, stratification criteria and response(s) to the targeted therapies described in the Projects. PMTC will closely interact with the Biostatistics and Bioinformatics and Functional Genomic Cores for genomic and functional analyses. The PMTC proposes 2 Specific Aims in support of all 4 Projects: (1) Generate and characterize PTDX and derived PDO and (2) provide comprehensive planning, preparation and coordination of in vivo PDTX co-clinical studies. Finally, after development, the Core will distribute PDTX tumors to PIs for mechanistic studies as needed (Project 3). Project Summary/Abstract Page 640

联系PD/PI: Rimsza， Lisa Shared-Res-Core-003 （458）