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Addressing biological and therapeutic gaps in rare neuroendocrine cancer with a novel organoid-based model

利用新型类器官模型解决罕见神经内分泌癌的生物学和治疗差距

基本信息

批准号：
10818715
负责人：
PATRICIA Leal DAHIA
金额：
$ 7.41万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-08 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10818715
关键词：
Address Adrenal Glands Attenuated Autonomic nervous system Award Biological Biological Models Biology Cells Chronic Citric Acid Cycle Clinical Management Congenital Heart Defects Detection Diagnosis Drug Screening Effectiveness Enzymes Event Experimental Models Future Genes Genetic Geometry Grant Growth Histologic Hydroxylation Hypoxia Hypoxia Pathway Investigation Knowledge Lead Light Malignant - descriptor Metastatic Pheochromocytoma Metastatic/Recurrent Methods Modeling Molecular Molecular Profiling Mutate Mutation Neoplasm Metastasis Neuroendocrine Tumors Organoids Oxygen Paraganglia structure Paraganglioma Parents Pathway interactions Patient-Focused Outcomes Patients Pattern Pharmaceutical Preparations Pheochromocytoma Population Primary Neoplasm Property Recurrence Regimen Regulation Reporting Resistance Resistance profile Resolution Risk Survival Rate Susceptibility Gene Testing Therapeutic Therapeutic Uses Tumor-Derived Ubiquitination Work anticancer research bHLH-PAS factor HLF clinical application design driver mutation drug sensitivity drug-sensitive effective therapy experimental study fitness human disease improved inhibitor innovation insight neuroendocrine cancer normoxia novel novel therapeutics parent grant potential biomarker predictive marker preference response screening single-cell RNA sequencing therapeutic evaluation transcription factor tumor

项目摘要

Abstract The work proposed on the parental grant is focused on developing new organoid models of rare and understudied neuroendocrine tumors pheochromocytomas and paragangliomas to improve our understanding of their biology and serve as a drug screen platform. Mutations in genes of the hypoxia pathway are a feature of approximately 40% of pheochromocytomas and paragangliomas and involve most metastatic forms of these tumors. In this diversity supplement we propose to extend the parent grant by testing the effects of hypoxia in the fitness and molecular features of the organoid cultures. We will also investigate whether hypoxia alters the organoids’ drug response profile. These findings will improve our knowledge of factors that influence organoid properties and may offer insights into drug sensitive/resistance patterns that might impact on future therapeutic testing.

摘要关于父母资助的建议工作重点是开发稀有和稀有的新的有机模型对神经内分泌瘤、嗜铬细胞瘤和副神经节瘤的研究不足，以提高我们的理解并作为药物筛选平台。低氧途径的基因突变是大约40%的嗜铬细胞瘤和副神经节瘤，并涉及这些肿瘤的大多数转移形式肿瘤。在这份多样性补充材料中，我们建议通过测试低氧对小鼠的影响来延长父母的补助金有机菌种的适合性和分子特征。我们还将调查缺氧是否会改变有机化合物的药物反应特征。这些发现将提高我们对影响有机化合物的因素的认识。属性，并可能提供对可能影响未来治疗的药物敏感/耐药模式的洞察测试。