RT Journal Article SR Electronic T1 Molecular Pathways: Targeting NRG1 Fusions in Lung Cancer JF Clinical Cancer Research JO Clin Cancer Res FD American Association for Cancer Research SP 1989 OP 1994 DO 10.1158/1078-0432.CCR-14-0854 VO 21 IS 9 A1 Fernandez-Cuesta, Lynnette A1 Thomas, Roman K. YR 2015 UL http://clincancerres.aacrjournals.org/content/21/9/1989.abstract AB The four members of the ERBB (HER) family of transmembrane receptor tyrosine kinases are frequently activated in cancer by several mechanisms, such as mutation, amplification, or autocrine ligand–receptor stimulation. We recently identified gene fusions involving the ERBB ligand gene, NRG1, which represent a novel mechanism for ERBB pathway deregulation. These fusions lead to expression and presentation of the EGF-like domain of NRG1 on the cell surface, which binds to ERBB3 in an autocrine and juxtacrine manner, thus inducing the formation of ERBB2–ERBB3 heterodimers, and subsequent activation of the PI3K–AKT and MAPK signaling pathways. These fusion genes were exclusively detected in lung adenocarcinomas of never smokers of the invasive mucinous subtype, which usually presents as a multifocal and unresectable disease, for which no effective treatment exists. Considering the large amount of drugs that target ERBB2 (HER2) and ERBB3 (HER3), and which are currently in different stages of clinical development, detecting and targeting NRG1 fusions in invasive mucinous lung adenocarcinomas may represent a therapeutic opportunity for this aggressive disease. Clin Cancer Res; 21(9); 1989–94. ©2014 AACR.