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YAP confers resistance to vandetanib in medullary thyroid cancer

Huan Wang1, Jian Tang2, Zhiwei Su1

  • 1Department of General Surgery, Jiaxing Maternity and Child Health Care Hospital, No. 2468 Central East Road, Nanhu District, Jiaxing 314000, Zhejiang, China.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|May 26, 2020
PubMed

Insights

Yes-Associated Protein (YAP) drives resistance to vandetanib in medullary thyroid cancer. Targeting YAP with an inhibitor alongside vandetanib shows promise for overcoming treatment resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Medullary thyroid cancer (MTC) is the third most common thyroid cancer.
  • Activating mutations in the Rearranged in Transformation (RET) gene are key drivers of MTC.
  • Vandetanib, a RET inhibitor, shows clinical promise but acquired resistance limits its efficacy.

Purpose of the Study:

  • To investigate the role of Yes-Associated Protein (YAP) in acquired resistance to vandetanib in MTC.
  • To explore YAP inhibition as a strategy to overcome vandetanib resistance.

Main Methods:

  • Generated a vandetanib-resistant MTC cell line (TT-R) from TT cells.
  • Assessed YAP's role in resistance using cell proliferation and colony formation assays.
  • Evaluated the combined antitumor effects of a YAP inhibitor and vandetanib in a xenograft mouse model.

Main Results:

  • TT-R cells exhibited a 6-fold higher IC50 to vandetanib compared to TT cells.
  • YAP overexpression conferred vandetanib resistance, while YAP knockdown restored sensitivity.
  • Combined treatment with a YAP inhibitor and vandetanib demonstrated synergistic tumor inhibition.

Conclusions:

  • YAP is a critical mediator of acquired vandetanib resistance in MTC.
  • Targeting YAP in combination with vandetanib presents a potential therapeutic strategy for MTC patients resistant to vandetanib.
Keywords:
YAPcancer médullaire de la thyroïdemedullary thyroid cancerresistancerésistancevandetanibvandétanib

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