Progress and challenges in experimental models for pheochromocytoma and paraganglioma.

IF 4.1 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Endocrine-related cancer Pub Date : 2023-04-04 Print Date: 2023-05-01 DOI:10.1530/ERC-22-0405
Arthur S Tischler, Judith Favier
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引用次数: 0

Abstract

Experimental models for pheochromocytoma and paraganglioma are needed for basic pathobiology research and for preclinical testing of drugs to improve treatment of patients with these tumors, especially patients with metastatic disease. The paucity of models reflects the rarity of the tumors, their slow growth, and their genetic complexity. While there are no human cell line or xenograft models that faithfully recapitulate the genotype or phenotype of these tumors, the past decade has shown progress in development and utilization of animal models, including a mouse and a rat model for SDH-deficient pheochromocytoma associated with germline Sdhb mutations. There are also innovative approaches to preclinical testing of potential treatments in primary cultures of human tumors. Challenges with these primary cultures include how to account for heterogeneous cell populations that will vary depending on the initial tumor dissociation and how to distinguish drug effects on neoplastic vs normal cells. The feasible duration for maintaining cultures must also be balanced against time required to reliably assess drug efficacy. Considerations potentially important for all in vitro studies include species differences, phenotype drift, changes that occur in the transition from tissue to cell culture, and the O2 concentration in which cultures are maintained.

嗜铬细胞瘤和副神经节瘤实验模型的进展和挑战。
嗜铬细胞瘤和副神经节瘤的实验模型是基础病理生物学研究和药物临床前测试所必需的,以改善这些肿瘤患者,特别是转移性疾病患者的治疗。模型的缺乏反映了肿瘤的罕见性、生长缓慢和遗传复杂性。虽然没有人细胞系或异种移植物模型能够忠实地再现这些肿瘤的基因型或表型,但过去十年在动物模型的开发和利用方面取得了进展,包括与种系Sdhb突变相关的SDH缺陷型嗜铬细胞瘤的小鼠和大鼠模型。在人类肿瘤的原代培养中,也有创新的方法来进行潜在治疗的临床前测试。这些原代培养的挑战包括如何解释异质性细胞群,这些细胞群将根据最初的肿瘤解离而变化,以及如何区分药物对肿瘤细胞和正常细胞的影响。维持培养物的可行持续时间也必须与可靠评估药物疗效所需的时间相平衡。对所有体外研究可能重要的考虑因素包括物种差异、表型漂移、从组织到细胞培养的过渡过程中发生的变化,以及维持培养的O2浓度。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Endocrine-related cancer
Endocrine-related cancer 医学-内分泌学与代谢
CiteScore
7.80
自引率
2.60%
发文量
138
审稿时长
6-12 weeks
期刊介绍: Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.
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