RET/PTC oncoproteins: Molecular targets of new drugs

Cinzia Lanzi, Giuliana Cassinelli, Giuditta Cuccuru, Chiara Zanchi, Diletta Laccabue, Franco Zunino

Research output: Contribution to journalArticle

Abstract

Ret oncoproteins expressed in thyroid carcinomas represent possible targets for therapeutic intervention. Oncogenic activation of the receptor tyrosine kinase encoding RET gene occurs typically by gene rearrangement in papillary thyroid carcinomas (PTC) and by missense mutation in medullary thyroid carcinomas (MTC). These genetic alterations lead to the expression of deregulated products characterized by ligand-independent activation of the intrinsic tyrosine kinase of Ret. Such features suggest the possibility of using specific tyrosine kinase inhibitors to block the Ret oncoproteins signaling. The present report summarizes the cellular effects of the arylidene 2-indolinone Ret inhibitor RPI-1 (formerly Cpd1) on the human PTC cell line TPC-1 which spontaneously harbors the RET/PTC1 oncogene. The results provide evidence that RPI-1 is able to inhibit cell growth and to interfere with RET/ PTC 1-driven signaling. These findings support a role for Ret oncoproteins as therapeutic targets and the pharmacological interest of RPI-1 as a candidate drug for preclinical evaluation on thyroid tumors expressing RET oncogenes.

Original languageEnglish
Pages (from-to)520-522
Number of pages3
JournalTumori
Volume89
Issue number5
Publication statusPublished - Sep 2003

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Keywords

  • 2-indolinone
  • Ret tyrosine kinase
  • Thyroid neoplasms

ASJC Scopus subject areas

  • Cancer Research

Cite this

Lanzi, C., Cassinelli, G., Cuccuru, G., Zanchi, C., Laccabue, D., & Zunino, F. (2003). RET/PTC oncoproteins: Molecular targets of new drugs. Tumori, 89(5), 520-522.