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Cancer Cell. 2011 Aug 16;20(2):158-72. doi: 10.1016/j.ccr.2011.07.011.

Neuregulin-1-mediated autocrine signaling underlies sensitivity to HER2 kinase inhibitors in a subset of human cancers.

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1
Massachusetts General Hospital Cancer Center and Harvard Medical School. Building 149, 13th Street, Charlestown, Boston, MA 02129, USA.

Abstract

HER2 kinase inhibitors, such as lapatinib, have demonstrated clinical efficacy in HER2-amplified breast cancers. By profiling nearly 700 human cancer cell lines, we identified a subset of non-HER2 amplified cancer cells with striking sensitivity to HER2 kinase inhibition-particularly from head and neck tumors. These cells were found to depend on a neuregulin-1 (NRG1)-mediated autocrine loop driving HER3 activation, which can be disrupted by lapatinib. Elevated NRG1 expression and activated HER3 are strongly associated with lapatinib sensitivity in vitro, and these biomarkers were enriched in a subset of primary head and neck cancer samples. The findings suggest that patients with NRG1-driven tumors lacking HER2 amplification may derive significant clinical benefit from HER2:HER3-directed therapies.

PMID:
21840482
DOI:
10.1016/j.ccr.2011.07.011
[Indexed for MEDLINE]
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