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RON confers lapatinib resistance in HER2-positive breast cancer cells

Quanren Wang1, Haitian Quan, Jie Zhao

  • 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Cancer Letters
|July 2, 2013
PubMed

Insights

Receptor tyrosine kinase (RTK) orphan 1 (RON) mediates lapatinib resistance in HER2-positive breast cancer. Targeting RON with inhibitors or siRNA can restore sensitivity to lapatinib by inhibiting PI3K/AKT activation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lapatinib resistance is a significant challenge in treating HER2-positive breast cancer.
  • The PI3K/AKT signaling pathway plays a crucial role in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the role of Receptor tyrosine kinase (RTK) orphan 1 (RON) in lapatinib resistance in HER2-positive breast cancer.
  • To evaluate the potential of targeting RON as a therapeutic strategy to overcome lapatinib resistance.

Main Methods:

  • Establishment of a lapatinib-resistant cell line (SK-BR-3-LR) from HER2-positive SK-BR-3 cells.
  • Assessment of PI3K/AKT signaling pathway activation in resistant cells.
  • Treatment with small-molecular RON inhibitors and RON-targeted small interfering RNA (siRNA).

Main Results:

  • The PI3K/AKT signaling pathway was resistant to HER2 inhibition in SK-BR-3-LR cells.
  • Both RON inhibitors and RON siRNA effectively restored lapatinib sensitivity in SK-BR-3-LR cells.
  • Inhibition of PI3K/AKT activation was observed following RON-targeted treatments.

Conclusions:

  • Receptor tyrosine kinase (RTK) orphan 1 (RON) plays a critical role in mediating lapatinib resistance in HER2-positive breast cancer.
  • Targeting RON presents a promising therapeutic strategy for patients who fail lapatinib treatment.
Keywords:
HER2HER2-targeted agentsLapatinib resistanceRON

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