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Cancer Lett. 2013 Oct 28;340(1):43-50. doi: 10.1016/j.canlet.2013.06.022. Epub 2013 Jun 27.

RON confers lapatinib resistance in HER2-positive breast cancer cells.

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

Abstract

Lapatinib-resistance is a major problem for HER2-positive breast cancer treatment. SK-BR-3-LR, a lapatinib-resistant cell clone, was established from HER2-positive SK-BR-3 breast cancer cells following chronic exposure to lapatinib. The PI3K/AKT signaling pathway was demonstrated to be resistant to HER2 inhibition in SK-BR-3-LR cells. However, both small-molecular Recepteur d'Origine Nantais (RON) inhibitors and RON-targeted small interfering RNA (siRNA) effectively restored lapatinib sensitivity in these cells by inhibiting PI3K/AKT activation. Our results demonstrate for the first time the important role of RON in mediating lapatinib resistance and suggest that RON-targeted therapy may become a novel, promising therapeutic strategy after the failure of lapatinib treatment in patients with HER2-positive breast cancer.

KEYWORDS:

HER2; HER2-targeted agents; Lapatinib resistance; RON

PMID:
23811285
DOI:
10.1016/j.canlet.2013.06.022
[Indexed for MEDLINE]
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