Hsu Kun-Tai, Yu Xiao-Min, Audhya Anjon W, Jaume Juan C, Lloyd Ricardo V, Miyamoto Shigeki, Prolla Tomas A, Chen Herbert
Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Endocrine Surgery Research Laboratories, Department of Surgery, Department of Biomolecular Chemistry, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Department of Pathology and Laboratory Medicine, Department of Oncology, Department of Genetics and Medical Genetics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
Oncologist. 2014 Nov;19(11):1148-55. doi: 10.1634/theoncologist.2014-0182. Epub 2014 Sep 26.
Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future.
间变性甲状腺癌（ATC）占所有甲状腺癌的比例不到2%，却导致了大多数甲状腺恶性肿瘤相关死亡，其生存期的中位数为6个月。ATC对包括放射性碘和促甲状腺激素抑制在内的传统甲状腺癌治疗具有抗性，这导致了这种恶性肿瘤的预后极差。本综述将涵盖几种细胞信号通路和机制，包括RET/PTC、RAS、BRAF、Notch、p53和组蛋白去乙酰化酶，这些已被确定在转化和去分化过程中发挥作用，以及针对这些通路的治疗方法。最后，还讨论了涉及Notch1通路、核因子κB、Trk融合基因、癌症干细胞样细胞、线粒体突变和肿瘤免疫微环境的新方法和药物。通过更好地理解生物学过程和治疗方式，有望在未来改善ATC的治疗结果。
