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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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RET tyrosine kinase signaling in development and cancer

Elena Arighi1, Maria Grazia Borrello, Hannu Sariola

  • 1Developmental Biology, Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Finland.

Cytokine & Growth Factor Reviews
|June 29, 2005
PubMed

Insights

RET receptor tyrosine kinase mutations cause diverse diseases, including cancers and Hirschsprung's disease. Understanding RET signaling is key to developing new treatments for thyroid cancer and MEN 2 syndrome.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • RET receptor tyrosine kinase mutations are linked to various human diseases, demonstrating significant phenotypic heterogeneity.
  • Gain-of-function RET mutations are implicated in human cancers, while loss-of-function mutations cause Hirschsprung's disease.

Purpose of the Study:

  • To review the role and mechanisms of RET signaling in both normal development and carcinogenesis.
  • To highlight the importance of understanding RET signaling for potential therapeutic development.

Main Methods:

  • Literature review of studies on RET receptor tyrosine kinase mutations and signaling pathways.
  • Analysis of genetic rearrangements and point mutations associated with specific diseases.

Main Results:

  • RET gene rearrangements create chimeric RET/PTC oncogenes in sporadic papillary thyroid carcinoma (PTC).
  • Germline RET point mutations cause multiple endocrine neoplasia types 2A and 2B (MEN 2A/2B) and familial medullary thyroid carcinoma (FMTC).
  • Both mutation types enhance RET tyrosine kinase activity, activating downstream targets.

Conclusions:

  • Dysregulation of RET signaling contributes to various cancers, particularly thyroid cancer.
  • Targeting RET signaling pathways offers potential therapeutic strategies for sporadic and inherited thyroid cancers and MEN 2 syndrome.

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