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Dasatinib and Trametinib Promote Anti-Tumor Metabolic Activity

Eric L Bolf1, Thomas C Beadnell1, Madison M Rose1

  • 1Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA.

Cells
|July 6, 2023
PubMed

Insights

Kinase inhibitors dasatinib and trametinib alter thyroid cancer cell metabolism, increasing tumor-suppressive 2-oxoglutarate. This metabolite reduces cancer cell viability, offering new therapeutic insights.

Area of Science:

  • Oncology
  • Biochemistry
  • Metabolomics

Background:

  • Thyroid cancer is the most common endocrine neoplasm.
  • Metastatic or radioiodine-refractory thyroid cancers have a poor prognosis.
  • Understanding therapeutic effects on cellular function is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the metabolic changes in thyroid cancer cells treated with kinase inhibitors.
  • To identify key metabolites affected by dasatinib and trametinib.
  • To evaluate the impact of identified metabolites on thyroid cancer cell viability.

Main Methods:

  • Treatment of thyroid cancer cells with dasatinib and trametinib.
  • Analysis of cellular metabolite profiles.
  • In vitro assessment of metabolite effects on cell viability.

Main Results:

  • Dasatinib and trametinib treatment altered glycolysis, the TCA cycle, and amino acid metabolism.
  • These kinase inhibitors induced a short-term accumulation of 2-oxoglutarate.
  • Elevated 2-oxoglutarate levels reduced thyroid cancer cell viability in vitro.

Conclusions:

  • Kinase inhibition significantly impacts the metabolome of thyroid cancer cells.
  • Reprogramming of metabolic processes by therapeutics influences cancer cell behavior.
  • Further research into therapeutic-induced metabolic alterations is needed for advanced thyroid cancer treatment.
Keywords:
MAPKSrccombinationdasatinibmetabolismmetabolomicsthyroid cancertrametinib

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