The RET proto-oncogene: a molecular therapeutic target in thyroid cancer

Cancer Sci. 2005 Mar;96(3):143-8. doi: 10.1111/j.1349-7006.2005.00023.x.


The RET proto-oncogene is responsible for the development of several human inherited and non-inherited diseases. Germline point mutations were identified in multiple endocrine neoplasia types 2A and 2B, and familial medullary thyroid carcinoma. More than 10 rearranged forms of RET, referred to as RET/PTC 1-9, ELKS/RET and RFP/RET, have been cloned from sporadic and radiation-associated papillary thyroid carcinomas. These mutations induced oncogenic activation of RET tyrosine kinase by different mechanisms. To date, various kinds of therapeutic approaches have been developed for the treatment of RET-associated cancers, including tyrosine kinase inhibitors, gene therapy with dominant negative RET mutants, and RNA interference to abrogate oncogenic mutant RET expression. RET and some signaling molecules that function downstream of RET could be potential targets for the development of selective cancer therapeutics.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Germ-Line Mutation
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / physiopathology
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / pharmacology
  • Proto-Oncogene Proteins c-ret
  • RNA Interference*
  • Receptor Protein-Tyrosine Kinases / biosynthesis
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Signal Transduction


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases