Targeting RET for thyroid cancer therapy

Cinzia Lanzi, Giuliana Cassinelli, Valentina Nicolini, Franco Zunino

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

The limited efficacy of conventional treatments in progressive thyroid carcinomas indicates the need for new therapeutic options. Activating mutations of the receptor tyrosine kinase-encoding RET gene have been identified as driving oncogenic events in subsets of papillary (PTC) and medullary (MTC) thyroid carcinomas suggesting the interest of targeted therapy. The role of RET oncogenes and the encoded constitutively active oncoproteins as potential targets has been investigated by different strategies including gene therapy and pharmacological approaches, but targeted treatment for RET-driven cancers is not clinically available in current therapy. Small molecule tyrosine kinase inhibitors, including sorafenib, sunitinib, motesanib and vandetanib, which have already shown efficacy against other neoplastic diseases, are being evaluated in clinical trials for treatment of thyroid carcinomas. Most of them, also described as Ret inhibitors, are multi-kinase inhibitors with antiangiogenic activity related to inhibition of receptor tyrosine kinases, such as the vascular endothelial growth factor receptors. Preclinical evidence supports the relevance of Ret oncoproteins as therapeutic targets for a subset of thyroid neoplastic diseases and, although targeting the original causal genetic change may not be sufficient to control the disease efficiently, the available knowledge outlines therapeutic opportunities for exploiting Ret inhibition.

Original languageEnglish
Pages (from-to)297-309
Number of pages13
JournalBiochemical Pharmacology
Volume77
Issue number3
DOIs
Publication statusPublished - Feb 1 2009

Fingerprint

Thyroid Neoplasms
Oncogene Proteins
Receptor Protein-Tyrosine Kinases
Gene therapy
Vascular Endothelial Growth Factor Receptor
Factor IX
Gene encoding
Protein-Tyrosine Kinases
Phosphotransferases
Therapeutics
Proto-Oncogene Proteins c-ret
Molecules
Thyroid Diseases
Oncogenes
Genetic Therapy
Clinical Trials
Pharmacology
Mutation
Genes
Neoplasms

Keywords

  • Protein tyrosine kinase
  • Ret
  • Targeted therapy
  • Thyroid carcinoma
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Targeting RET for thyroid cancer therapy. / Lanzi, Cinzia; Cassinelli, Giuliana; Nicolini, Valentina; Zunino, Franco.

In: Biochemical Pharmacology, Vol. 77, No. 3, 01.02.2009, p. 297-309.

Research output: Contribution to journalArticle

Lanzi, C, Cassinelli, G, Nicolini, V & Zunino, F 2009, 'Targeting RET for thyroid cancer therapy', Biochemical Pharmacology, vol. 77, no. 3, pp. 297-309. https://doi.org/10.1016/j.bcp.2008.10.033
Lanzi, Cinzia ; Cassinelli, Giuliana ; Nicolini, Valentina ; Zunino, Franco. / Targeting RET for thyroid cancer therapy. In: Biochemical Pharmacology. 2009 ; Vol. 77, No. 3. pp. 297-309.
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