RET Tyrosine Kinase and Medullary Thyroid Cells are Unaffected by Clinical Doses of STI571

Michael A. Skinner, Shawn D. Safford, Alex J. Freemerman

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Background: Activating mutations in the RET receptor tyrosine kinase are responsible for the development of medullary thyroid cancer (MTC) in persons with Multiple Endocrine Neoplasia type 2. We hypothesized that STI571 (Gleevec) would inhibit RET kinase and be a useful agent in the treatment of MTC. Materials and Methods: We determined the IC50 of STI571 for RET using an in vitro kinase assay and also examined the effects of STI571 on cellular proliferation and viability in TT cells, a human MTC cell line. Results: The average in vitro IC50 of STI571 for RET is 37 μM ± 4 μM. Additionally, TT cells incubated with 10 μM STI571 for up to 8 days showed no apparent reduction in cell proliferation or viability. Higher concentrations of STI571, from 25 to 100 μM, induced necrosis of TT cells. Conclusion: The concentrations of STI571 required to significantly inhibit RET and to inhibit TT cell proliferation are not clinically achievable. We conclude that STI571 is not likely to be an effective treatment for MTC.

Original languageEnglish (US)
Pages (from-to)3601-3606
Number of pages6
JournalAnticancer Research
Issue number5 A
StatePublished - Sep 2003

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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