1 Anaplastic Thyroid Cancer: Molecular Pathogenesis and 1 Emerging Therapies (Review) 2 3

Abstract 1 Anaplastic thyroid cancer (ATC) is a rare malignancy. While external beam radiation therapy 2 has improved locoregional control, the median survival of approximately four months has not 3 changed in more than half a century due to uncontrolled systemic metastases. The objective of 4 this study was to review the literature in order to identify potential new strategies for treating this 5 highly lethal cancer. PubMed searches were the principal source of articles reviewed. The 6 molecular pathogenesis of ATC includes mutations in BRAF, RAS, β-catenin, PIK3CA, p53, 7 AXIN, PTEN and APC genes, and chromosomal abnormalities are common. Several microarray 8 studies have identified genes and pathways preferentially affected, and dysregulated microRNA 9 profiles differ from differentiated thyroid cancers. Numerous proteins involving transcription 10 factors, signaling pathways, mitosis, proliferation, cell cycle, apoptosis, adhesion, migration, 11 epigenetics, and protein degradation are affected. A variety of agents have been successful in 12 controlling ATC cell growth both in vitro and in nude mice xenografts. While many of these 13 new compounds are in cancer clinical trials, there are few studies being conducted in ATC. With 14 the recent increased knowledge of the many critical genes and proteins affected in anaplastic 1