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

摘要 在父母补助金上提出的工作重点是开发新的罕见的类器官模型， 神经内分泌肿瘤、嗜铬细胞瘤和副神经节瘤的研究不足， 并作为药物筛选平台。缺氧途径基因的突变是 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 肿瘤的在这个多样性的补充，我们建议延长父母补助金，通过测试缺氧的影响， 类器官培养物的适应性和分子特征。我们还将研究缺氧是否会改变 类器官的药物反应曲线这些发现将提高我们对影响类器官的因素的认识 特性，并可能提供对可能影响未来治疗的药物敏感/耐药模式的见解 试验.

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.