Radiogenomic Credentialing of Head and Neck Cancer Models

头颈癌模型的放射基因组学认证

基本信息

批准号：
10529301
负责人：
Mukund Seshadri
金额：
$ 58.38万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10529301
关键词：
Adrenergic beta-Antagonists Allografting Appearance Autologous Bioinformatics Biological Models Biology Cancer Model Cetuximab Cisplatin Clinical Coculture Techniques Collaborations Comprehensive Cancer Center Credentialing Critical Pathways Critiques Data Development Disease Dissection Drug Screening Evaluation Exhibits FDA approved Functional Imaging Future Gene Expression Profile Genomics Goals Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Heterogeneity Histone Deacetylase Inhibitor Human Human Papillomavirus Immunocompetent Immunological Models In Vitro Investigation Malignant Neoplasms Mediating Modeling Molecular Molecular Profiling Multimodal Imaging Mus Mutation Neoplasms Organoids Pathogenesis Patients Pharmaceutical Preparations Propranolol Publishing Quality of life Radiation Radiation therapy Radiogenomics Radiology Specialty Research Personnel Resistance Respiratory physiology Safety Siblings Speech System T-Lymphocyte Testing Therapeutic Therapeutic Trials Treatment Efficacy Treatment Protocols Validation Valproic Acid Work Xenograft procedure biobank biomarker discovery cancer imaging chemoradiation comparative drug candidate drug efficacy drug repurposing efficacy evaluation experience high-throughput drug screening human disease image guided imaging biomarker imaging modality immune checkpoint blockade immunological status immunoregulation in vivo in vivo Model innovation insight mouse model multimodality novel novel strategies novel therapeutics patient derived xenograft model patient population patient response pre-clinical precision medicine radiation response research clinical testing resistance mechanism response screening standard of care targeted agent transcriptome sequencing treatment response treatment strategy tumor tumor immunology tumor xenograft

项目摘要

Abstract Head and neck squamous cell carcinomas (HNSCC) are aggressive neoplasms that result in debilitating changes in speech, appearance, and quality of life in humans. Response rates in HNSCC patients have remained relatively unchanged over the years, especially in patients with human papillomavirus (HPV) negative HNSCC highlighting the critical need for novel strategies to meet the therapeutic needs of this patient population. As recognized by PAR-17-245, a critical step in discovering novel therapies for HNSCC patients is the development of tumor models that can reliably recapitulate human disease biology, heterogeneity and therapeutic response. The overall goal of this application is to validate and credential a panel of patient- derived and immunocompetent models of HNSCC. Systematic and in-depth comparison of histopathologic, genomic, and therapeutic response profiles will be performed across multiple preclinical platforms in vitro (organoids) and in vivo (allografts/xenografts). Paired in vitro and in vivo models across these platforms will be used to assess their response to standard of care chemoradiation and immune checkpoint blockade. The models will also be used to screen the activity of novel and FDA-approved agents (‘drug repurposing’) targeting critical pathways implicated in the pathogenesis of HNSCC. The application builds on an existing collaboration between several investigators at Roswell Park Comprehensive Cancer Center with extensive experience and expertise in mammalian models, head and neck cancer, cancer imaging, tumor immunology, genomics, bioinformatics and cancer therapeutics. The project will employ innovative multimodal functional imaging methods to better define and enhance the true translational utility of mammalian models. The proposal will establish a robust panel of credentialed mammalian models of HNSCC and enable development of an integrated preclinical pipeline to assess efficacy of novel therapeutics, identify resistance mechanisms and enable biomarker discovery in HNSCC.

抽象的头颈鳞状细胞癌 (HNSCC) 是一种新的侵袭性血浆，会导致患者衰弱 HNSCC 患者的言语、外观和生活质量发生了变化。多年来保持相对不变，特别是在人乳头瘤病毒（HPV）患者中 HNSCC 阴性表明迫切需要新的策略来满足该患者的治疗需求正如 PAR-17-245 所认识到的，发现 HNSCC 患者新疗法的关键一步是开发能够可靠地概括人类疾病生物学、异质性和该治疗应用的总体目标是验证和验证一组患者的反应。 HNSCC 的衍生模型和免疫功能模型的组织病理学、基因组和治疗反应概况将在体外多个临床前平台上进行（类器官）和体内（同种异体移植/异种移植）将在这些平台上配对体外和体内模型。用于评估他们对护理标准放化疗和免疫检查点封锁的反应。模型还将用于筛选 FDA 批准的新型药物的活性（“药物再利用”）该应用程序建立在现有的基础上。罗斯威尔公园综合癌症中心的几位研究人员之间进行了广泛的合作在哺乳动物模型、头颈癌、癌症成像、肿瘤免疫学、该项目将采用创新的多模式功能学。成像方法可以更好地定义和增强哺乳动物模型的真正转化效用。将建立一个强大的、经过认证的 HNSCC 哺乳动物模型组，并能够开发综合临床前管道，以评估新疗法的功效、识别耐药机制和促进 HNSCC 中生物标志物的发现。