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Sunitinib inhibits papillary thyroid carcinoma with RET/PTC rearrangement but not BRAF mutation

Woo-Jin Jeong1, Ji-Hun Mo, Min Woo Park

  • 1Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

Cancer Biology & Therapy
|July 5, 2011
PubMed

Insights

Sunitinib effectively inhibits papillary thyroid cancer cells with RET/PTC rearrangement but not BRAF mutations. This suggests sunitinib targets the MAPK pathway, impacting treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Sunitinib is a multi-targeted tyrosine kinase inhibitor used for refractory papillary thyroid carcinoma.
  • Its precise mechanism in papillary thyroid carcinoma, especially concerning BRAF mutations, remains unclear.

Purpose of the Study:

  • To investigate sunitinib's effect on papillary thyroid carcinoma cells with RET/PTC rearrangement versus BRAF mutations.
  • To elucidate the underlying molecular mechanisms of sunitinib's action.

Main Methods:

  • Utilized TPC-1M, SNU-790, and B-cPAP cell lines representing RET/PTC and BRAF mutations.
  • Performed cell growth inhibition assays, immunoblotting for MEK/ERK pathway, and cell cycle analysis.
  • Evaluated tumor growth inhibition in an in vivo orthotopic mouse model.

Main Results:

  • Sunitinib effectively inhibited RET/PTC rearrangement cells at low doses (IC50=0.658 μM), while BRAF mutated cells required higher doses.
  • MEK/ERK pathway was blocked in RET/PTC cells but not in BRAF mutated cells.
  • G1 cell cycle arrest was observed in RET/PTC rearrangement cells; significant tumor growth inhibition occurred in vivo.

Conclusions:

  • Sunitinib demonstrates efficacy against RET/PTC rearranged papillary thyroid carcinoma cells, not BRAF mutated cells.
  • The drug likely inhibits the upstream MAPK signaling cascade.
  • Findings may explain varied clinical trial outcomes and guide sunitinib's application.

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