Medullary thyroid cancer: a promising model for targeted therapy

Rosa Maria Paragliola, Salvatore Maria Corsello, Francesco Torino, Agnese Barnabei

Risultato della ricerca: Contributo in rivistaArticolo in rivista

13 Citazioni (Scopus)

Abstract

In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET receptor TK and its signal transduction pathways, lead to subsequent neoplastic transformation. Several strategies aimed at blocking the activation and signaling of RET have been preclinically tested. The most advanced results have been obtained by competitive inhibition of RET-TK activity by tyrosine kinases inhibitors (TKI). However, although the inhibition of the RET pathway is actually one of the most studied for therapeutic purposes, other signal transduction pathways have been recognized to contribute to the growth and functional activity of MTC and are considered attractive therapeutic targets. To date, surgery represents the only curative treatment of MTC. Despite promising initial results, studies on targeted agents are in early stages and several issues regarding preclinical evaluations and clinical trials of new targeted agents in MTC are still unresolved. Now, available mouse models bearing mutations of RET or other genes, which spontaneously develop MTC, promise to improve preclinical evaluation of activity of targeted compounds. Furthermore, the rarity of the disease and the number of patients available for enrollment may lessen the relevance of clinical trials. A major effort needs to be made by endocrinologists and oncologists to refer their patients for multi-institutional trials in order to optimize them, perform translational studies and expedite the availability of novel beneficial selective therapies.
Lingua originaleEnglish
pagine (da-a)608-625
Numero di pagine18
RivistaCurrent Molecular Medicine
Volume10
Stato di pubblicazionePubblicato - 2010

Keywords

  • Animals
  • Antineoplastic Agents
  • Carcinoma
  • Carcinoma, Medullary
  • Humans
  • Mice
  • Molecular Targeted Therapy
  • Multiple Endocrine Neoplasia
  • Neoplastic Syndromes, Hereditary
  • Protein Kinase Inhibitors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • Signal Transduction
  • Thyroid Neoplasms

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