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Thyroid carcinoma: molecular pathways and therapeutic targets

Yuri E Nikiforov1

  • 1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA. nikiforovye@upmc.edu

Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
|June 24, 2008
PubMed

Insights

Thyroid cancer, the most common endocrine malignancy, often involves genetic mutations activating the MAPK pathway. These mutations, common in papillary and follicular types, are key targets for new cancer therapies currently in clinical trials.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Thyroid cancer is the most prevalent endocrine malignancy.
  • Papillary thyroid carcinoma is the most common subtype, frequently driven by genetic alterations.
  • Key signaling pathways, like the mitogen-activated protein kinase (MAPK) pathway, are often dysregulated in thyroid tumors.

Purpose of the Study:

  • To review common genetic alterations in various thyroid cancer types.
  • To highlight the role of MAPK pathway activation in thyroid tumorigenesis.
  • To discuss the therapeutic potential of targeting these genetic alterations.

Main Methods:

  • Review of genetic alterations in papillary, follicular, and medullary thyroid carcinomas.
  • Analysis of common mutations (BRAF, RAS) and rearrangements (RET/PTC, PAX8-PPARgamma).
  • Examination of the prevalence and overlap of these alterations.
  • Overview of therapeutic strategies targeting MAPK pathway activation.

Main Results:

  • BRAF point mutations, RAS mutations, and RET/PTC rearrangement are prevalent in papillary thyroid carcinoma (>70%), rarely overlapping.
  • RAS mutations and PAX8-PPARgamma rearrangement are common in follicular thyroid carcinoma.
  • RET point mutations are critical in medullary thyroid carcinoma development.
  • Many identified mutations activate the MAPK pathway.

Conclusions:

  • Specific genetic alterations are characteristic of different thyroid cancer subtypes.
  • MAPK pathway activation is a common mechanism in thyroid cancer development.
  • Targeting these mutations represents a promising therapeutic avenue, with several compounds in clinical trials.

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