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Targeting RET for thyroid cancer therapy.

Cinzia Lanzi1, Giuliana Cassinelli, Valentina Nicolini

  • 1Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133 Milan, Italy.

Biochemical Pharmacology
|November 26, 2008
PubMed
Summary

New targeted therapies are needed for progressive thyroid cancers. Research explores RET oncogenes and tyrosine kinase inhibitors, showing promise for future RET-driven cancer treatments.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Conventional treatments for progressive thyroid carcinomas show limited efficacy.
  • Activating mutations in the RET gene drive oncogenesis in papillary (PTC) and medullary (MTC) thyroid carcinomas.
  • Targeted therapies for RET-driven thyroid cancers are not yet clinically available.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting RET oncogenes in thyroid carcinomas.
  • To evaluate the efficacy of small molecule tyrosine kinase inhibitors (TKIs) as a targeted treatment strategy.
  • To explore the role of RET oncoproteins as therapeutic targets for subsets of thyroid neoplastic diseases.

Main Methods:

  • Review of preclinical evidence and ongoing clinical trials for RET-targeted therapies.
  • Investigation of pharmacological approaches, including multi-kinase inhibitors with antiangiogenic activity.
  • Assessment of small molecule TKIs such as sorafenib, sunitinib, motesanib, and vandetanib.

Main Results:

  • Preclinical data support RET oncoproteins as relevant therapeutic targets for specific thyroid cancers.
  • Multi-kinase inhibitors targeting RET also exhibit antiangiogenic activity via inhibition of vascular endothelial growth factor receptors.
  • Clinical trials are evaluating the efficacy of several TKIs in thyroid carcinoma treatment.

Conclusions:

  • Targeting RET inhibition presents therapeutic opportunities for RET-driven thyroid neoplastic diseases.
  • While targeting the initial genetic alteration may not be fully sufficient, RET inhibition is a promising strategy.
  • Further development of targeted treatments for RET-driven thyroid cancers is warranted.