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Mechanistic Insights of Thyroid Cancer Progression

Luis Javier Leandro-García1, Iñigo Landa2

  • 1Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.

Endocrinology
|July 28, 2023
PubMed

Insights

This review details key genetic mutations driving thyroid cancer progression from differentiated to aggressive forms. Understanding these alterations is crucial for developing targeted therapies and improving patient outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Differentiated thyroid cancers (DTCs) originate from MAPK pathway mutations (BRAF, RAS).
  • Thyroid cancer progression to poorly differentiated (PDTC) and anaplastic (ATC) forms involves accumulating genetic alterations.
  • Identifying key mutations is vital for understanding thyroid cancer evolution and treatment resistance.

Approach:

  • Comprehensive review of literature over two decades focusing on bona fide mutations in thyroid cancer progression.
  • Analysis of genetic alterations with robust mechanistic data in PDTC/ATC.
  • Examination of functional data from in vitro and in vivo models for specific genes and pathways.

Key Points:

  • TP53 mutations, PI3K/AKT pathway effectors, TERT promoter mutations, SWI/SNF complex alterations, NF2, and EIF1AX are significantly enriched in aggressive thyroid cancers.
  • Mechanistic data supports the role of these genetic alterations in thyroid cancer progression.
  • Other genetic changes in aggressive tumors are noted, though mechanistic data may be limited.

Conclusions:

  • Preclinical studies are essential for translating genomic insights into clinical applications for thyroid cancer.
  • Targeting specific genetic pathways identified in this review holds promise for novel therapeutic strategies.
  • Further research into less-understood genetic alterations could uncover new therapeutic targets for advanced thyroid cancers.
Keywords:
anaplastic thyroid cancercancer genomicscancer progressionmouse modelspapillary thyroid cancerthyroid cancer pathogenesis

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