@article{8fd0c373f479438d8eebf6eaeb375896,
title = "Targeting ADAM-mediated ligand cleavage to inhibit HER3 and EGFR pathways in non-small cell lung cancer",
abstract = "We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC cell lines. A selective ADAM inhibitor, INCB3619, prevents the processing and activation of multiple ErbB ligands, including heregulin. In addition, INCB3619 inhibits gefitinib-resistant HER3 signaling and enhances gefitinib inhibition of EGFR signaling in NSCLC. These results show that ADAM inhibition affects multiple ErbB pathways in NSCLC and thus offers an excellent opportunity for pharmacological intervention, either alone or in combination with other drugs.",
keywords = "SIGNALING",
author = "Zhou, {Bin Bing S} and Michael Peyton and Biao He and Changnian Liu and Luc Girard and Eian Caudler and Yvonne Lo and Frederic Baribaud and Iwao Mikami and Noemi Reguart and Gengjie Yang and Yanlong Li and Wenqing Yao and Kris Vaddi and Gazdar, {Adi F.} and Friedman, {Steven M.} and Jablons, {David M.} and Newton, {Robert C.} and Fridman, {Jordan S.} and Minna, {John D.} and Scherle, {Peggy A.}",
note = "Funding Information: We gratefully acknowledge Dr. Xiangdong Liu and Mr. Mike Hansbury for helpful discussion and generous technical help during the course of this work, and Dr. Philip Liu for advice and technical help with siRNA experiments. We thank Drs. Kermit Carraway, Cary Lai, David Nethery, and Ruth Lupu for helpful advice on the heregulin experiments. The work in J.D.M.'s group was supported by Lung Cancer SPORE grant P50CA70907 and the Gilson Longenbaugh Foundation. The work in D.M.J.'s group was supported by the Larry Hall Memorial Trust and the Kazan, McClain, Edises, Abrams, Fernandez, Lyons & Farrise Foundation. Authors affiliated with Incyte declare competing financial interests. ",
year = "2006",
month = jul,
doi = "10.1016/j.ccr.2006.05.024",
language = "English (US)",
volume = "10",
pages = "39--50",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "1",
}