Cancer Molecular Pathology, School of Medicine, Griffith University, Gold Coast Campus, Gold Coast, QLD, 4222, Australia.
Department of Endocrinology and Diabetes Mellitus, Fukuoka University Chikushi Hospital, Chikushino, Fukuoka, 818-8502, Japan.
Curr Oncol Rep. 2021 Feb 13;23(3):31. doi: 10.1007/s11912-021-01019-9.
Anaplastic thyroid carcinoma is a type of thyroid carcinoma with the most aggressive biological behaviour amongst thyroid cancer. Here, we review the current genomic and the impacts of advances in therapies to improve the management of patients with the cancer.
Common mutations being identified in anaplastic thyroid carcinoma are p53 and TERT promoter mutations. Other common mutated genes included BRAF, RAS, EIF1AX, PIK3CA, PTEN and AKT1, SWI/SNF, ALK and CDKN2A. Changes in expression of different microRNAs are also involved in the pathogenesis of anaplastic thyroid carcinoma. Curative resection combined with radiotherapy and combination chemotherapies (such as anthracyclines, platins and taxanes) has been shown to have effects in the treatment of some patients with anaplastic thyroid carcinoma. Newer molecular targeted therapies in clinical trials target mostly the cell membrane kinase and downstream proteins. These include targeting the EGFR, FGFR, VEGFR, c-kit, PDGFR and RET on the cell membrane as well as VEGF itself and the downstream targets such as BRAF, MEK and mTOR. Immunotherapy is also being tested in the cancer. Updated knowledge of genomic as well as clinical trials on novel therapies is needed to improve the management of the patients with this aggressive cancer.
间变性甲状腺癌是一种甲状腺癌,其生物学行为在所有甲状腺癌中最为激进。本文就目前间变性甲状腺癌的基因组学研究进展,以及这些进展对改善癌症患者治疗效果的影响进行综述。
在间变性甲状腺癌中常见的突变是 p53 和 TERT 启动子突变。其他常见的突变基因包括 BRAF、RAS、EIF1AX、PIK3CA、PTEN 和 AKT1、SWI/SNF、ALK 和 CDKN2A。不同 microRNAs 的表达变化也参与了间变性甲状腺癌的发病机制。有研究表明,根治性切除术联合放疗和联合化疗(如蒽环类、铂类和紫杉烷类)对某些间变性甲状腺癌患者有效。临床试验中新型分子靶向治疗的靶点主要是细胞膜激酶及其下游蛋白。这些靶点包括细胞膜上的 EGFR、FGFR、VEGFR、c-kit、PDGFR 和 RET,以及 VEGF 本身及其下游靶点,如 BRAF、MEK 和 mTOR。免疫疗法也在该癌症中进行了测试。为了改善这种侵袭性癌症患者的治疗效果,需要了解最新的基因组学知识以及新型治疗方法的临床试验结果。