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Is transketolase like 1 a target for the treatment of differentiated thyroid carcinoma? A study on thyroid cancer

Eleonore Fröhlich1, Inge Fink, Richard Wahl

  • 1Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Internal Medicine, University of Tuebingen, Tuebingen, Germany.

Investigational New Drugs
|September 23, 2008
PubMed

Insights

Transketolase like 1 (TKTL-1) is overexpressed in aggressive thyroid cancers. However, TKTL-1 expression does not predict response to oxythiamine, suggesting a need for more targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Radioactive iodine-refractory thyroid carcinomas are aggressive and often glucose-avid.
  • Targeting glucose metabolism is a potential therapeutic strategy.
  • Transketolase like 1 (TKTL-1), a transketolase isoenzyme, is overexpressed in various cancers.

Purpose of the Study:

  • To investigate the correlation between TKTL-1 expression and the response to oxythiamine in differentiated thyroid cancer cell lines.
  • To evaluate TKTL-1 as a potential biomarker for oxythiamine efficacy.

Main Methods:

  • Differentiated thyroid cancer cell lines were analyzed for TKTL-1 expression, proliferation, and glucose uptake.
  • The effect of oxythiamine on iodide and thymidine uptake was assessed.
  • GLUT-1 expression was also determined.

Main Results:

  • TKTL-1 expression was highest in cell lines from more invasive tumors.
  • TKTL-1 expression levels did not strongly correlate with proliferation rate, GLUT-1 expression, or response to oxythiamine.
  • Oxythiamine demonstrated only a weak inhibitory effect in TKTL-1 expressing cell lines.

Conclusions:

  • Overexpression of TKTL-1 is not a reliable indicator of responsiveness to oxythiamine in differentiated thyroid cancer.
  • More specific inhibitors targeting TKTL-1 or related pathways need to be investigated for therapeutic efficacy.

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