Molecular aberrations and signaling cascades implicated in the pathogenesis of anaplastic thyroid cancer

Biochim Biophys Acta Rev Cancer. 2019 Dec;1872(2):188262. doi: 10.1016/j.bbcan.2018.12.003. Epub 2018 Dec 31.

Abstract

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.

Keywords: Anaplastic thyroid cancer; Inhibitors; Mutations; Signaling; Therapeutics; Tumor.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Chromosome Aberrations
  • Epigenesis, Genetic
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Mutation
  • Signal Transduction
  • Thyroid Carcinoma, Anaplastic / genetics*
  • Thyroid Neoplasms / genetics*