Molecular aberrations and signaling cascades implicated in the pathogenesis of anaplastic thyroid cancer.
Molecular aberrations and signaling cascades implicated in the pathogenesis of anaplastic thyroid cancer.
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DOI：
10.1016/j.bbcan.2018.12.003
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Shikha Saini;A. Maker;K. Burman;B. Prabhakar
中科院分区：
文献类型：
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作者：
Shikha Saini;A. Maker;K. Burman;B. Prabhakar
间变性甲状腺癌（ATC）占甲状腺癌相关死亡的40%以上，预后不良。在过去的十年中，已经做出了重大努力，以了解这种疾病的发病机制和开发新的治疗方法。不幸的是，有效的治疗仍然缺乏和更彻底的了解ATC的发病机制可能提供新的机会，以改善ATC治疗。本文综述了ATC的临床表现和病理学，以及遗传畸变和分子信号通路改变在ATC发病机制中的作用。我们综述了ATC中普遍存在的突变、染色体异常和融合、表观遗传学改变和失调，并强调了ATC发病机制中不可或缺的几个信号级联。此外，这些特征提供了对ATC的去分化、侵袭性和耐药表型的见解，因此可能有助于探索用于开发新疗法的潜在新分子靶点。
Anaplastic Thyroid Cancer (ATC) accounts for >40% thyroid cancer-related deaths and has a dismal prognosis. In the past decade, significant efforts have been made towards understanding the pathogenesis of this disease and developing novel therapeutics. Unfortunately, effective treatment is still lacking and a more thorough understanding of ATC pathogenesis may provide new opportunities to improve ATC therapeutics. This review provides insights into ATC clinical presentation and pathology, and the putative role of genetic aberrations and alterations in molecular signaling pathways in ATC pathogenesis. We reviewed prevalent mutations, chromosomal abnormalities and fusions, epigenetic alterations and dysregulations in ATC, and highlighted several signaling cascades which appeared to be integral to ATC pathogenesis. Moreover, these features offer insights into de-differentiated, aggressive and drug-resistant phenotype of ATC, and thus may help in exploring potential new molecular targets for developing novel therapeutics.