Identification of RET kinase inhibitors as potential new treatment for sporadic and inherited thyroid cancer

J Chemother. 2004 Nov:16 Suppl 4:49-51. doi: 10.1179/joc.2004.16.Supplement-1.49.

Abstract

The RET gene is frequently mutated in papillary thyroid carcinoma and in medullary thyroid carcinoma. We have identified three different anti-RET drugs: two pyrazolo-pyrimidines, PP1 and PP2 and an anilinoquinazoline, ZD6474 (AstraZeneca). These compounds are able to inhibit RET kinase activity in vitro (IC50 dose 100 nM) and in vivo and they can prevent RET mediated transformation. Finally, mutation of RET V804 to methionine or leucine, found in MTC patients, induces resistance to the three drugs.

Publication types

  • Comparative Study

MeSH terms

  • Carcinoma, Medullary / drug therapy
  • Carcinoma, Medullary / genetics
  • Carcinoma, Papillary / drug therapy
  • Carcinoma, Papillary / genetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Mutation
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / drug effects
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Sensitivity and Specificity
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Treatment Outcome

Substances

  • Piperidines
  • Proto-Oncogene Proteins
  • Quinazolines
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • vandetanib