Department of Cell Developmental and Regenerative Biology, School of Biomedical Sciences, Icahn School of Medicine, New York, New York, USA.
Department of Cell Developmental and Regenerative Biology, School of Biomedical Sciences, Icahn School of Medicine, New York, New York, USA
Endocr Relat Cancer. 2018 Feb;25(2):T91-T104. doi: 10.1530/ERC-17-0411.
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 and (fish and fly) models.
25 年前，RET 被确定为多发性内分泌肿瘤 2 型（MEN2）综合征的主要驱动因素。MEN2 的特征是包括嗜铬细胞瘤、甲状旁腺腺瘤和更具侵袭性的甲状腺髓样癌（MTC）等多种转化事件。总的来说，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、放疗、放射性核素治疗和化疗都显示出有限的成功，在晚期疾病中，这些方法都没有证明是持久的。整合了与 MEN2 和其他与 RET 相关疾病相关的致癌性 RET 异构体的非哺乳动物模型在阐明疾病进展的机制方面非常有用。这些模型还确定了新的靶向治疗药物作为单一药物以及联合药物。这些研究强调了在整个动物背景下对疾病进行建模的重要性，考虑到肿瘤和正常细胞之间的复杂相互作用，以控制疾病进展以及对治疗的反应。随着对扩大的甲状腺癌患者队列的全基因组测序数据的方便获取，非哺乳动物模型将变得更加复杂、复杂，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包括 MTC 在内的甲状腺癌的贡献，重点关注鱼类和果蝇模型。
