Non-mammalian models of multiple endocrine neoplasia type 2.
Non-mammalian models of multiple endocrine neoplasia type 2.
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DOI：
10.1530/erc-17-0411
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发表时间：
2018-03
影响因子：
3.9
通讯作者：
Cagan RL
中科院分区：
文献类型：
--
作者：
Das TK;Cagan RL
二十五年前，RET 被确定为 2 型多发性内分泌肿瘤 (MEN2) 综合征的主要驱动因素。 MEN2 的特征是多种转化事件，包括嗜铬细胞瘤、甲状旁腺腺瘤，尤其是渗透性甲状腺髓样癌 (MTC)。总体而言，MTC 是一种罕见但具有侵袭性的甲状腺癌，目前尚无有效的治疗方法。手术、放射、放射性同位素治疗和化疗都显示出有限的成功，并且这些方法都没有被证明对晚期疾病具有持久性。纳入与 MEN2 和其他 RET 相关疾病相关的致癌 RET 同工型的非哺乳动物模型已有助于描绘疾病进展的机制。这些模型还确定了新的靶向疗法作为单一药物和组合。这些研究强调了在整个动物的背景下建模疾病的重要性，解释了肿瘤和正常细胞在控制疾病进展以及对治疗的反应中复杂的相互作用。通过方便地获取来自扩大的甲状腺癌患者群体的全基因组测序数据，非哺乳动物模型将变得更加复杂、精密，并继续补充未来的哺乳动物研究。在这篇综述中，我们探讨了非哺乳动物模型对我们理解甲状腺癌（包括 MTC）的贡献，重点关注斑马鱼和果蝇（鱼和蝇）模型。
Twenty-five years ago, RET was identified as the primary driver of Multiple Endocrine Neoplasia Type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment, and chemotherapeutics have all shown limited success and none of these approaches have proven durable in advanced disease. Non-mammalian models that incorporate the oncogenic RET isoforms associated with MEN2 and other RET-associated diseases have been useful in delineating mechanisms underlying disease progression. These models have also identified novel targeted therapies as single agents and as combinations. These studies highlight the importance of modeling disease in the context of the whole animal, accounting for the complex interplay between tumor and normal cells in controlling disease progression, as well as response to therapy. With convenient access to whole genome sequencing data from expanded thyroid cancer patient cohorts, non-mammalian models will become more complex, sophisticated and continue to complement future mammalian studies. In this review we explore the contributions of non-mammalian models to our understanding of thyroid cancer including MTC, with a focus on Danio rerio and Drosophila melanogaster—fish and fly—models.