RT Journal Article SR Electronic T1 EGFR Fusions as Novel Therapeutic Targets in Lung Cancer JF Cancer Discovery JO Cancer Discov FD American Association for Cancer Research SP 601 OP 611 DO 10.1158/2159-8290.CD-16-0075 VO 6 IS 6 A1 Konduri, Kartik A1 Gallant, Jean-Nicolas A1 Chae, Young Kwang A1 Giles, Francis J. A1 Gitlitz, Barbara J. A1 Gowen, Kyle A1 Ichihara, Eiki A1 Owonikoko, Taofeek K. A1 Peddareddigari, Vijay A1 Ramalingam, Suresh S. A1 Reddy, Satyanarayan K. A1 Eaby-Sandy, Beth A1 Vavalà, Tiziana A1 Whiteley, Andrew A1 Chen, Heidi A1 Yan, Yingjun A1 Sheehan, Jonathan H. A1 Meiler, Jens A1 Morosini, Deborah A1 Ross, Jeffrey S. A1 Stephens, Philip J. A1 Miller, Vincent A. A1 Ali, Siraj M. A1 Lovly, Christine M. YR 2016 UL http://cancerdiscovery.aacrjournals.org/content/6/6/601.abstract AB Here, we report that novel epidermal growth factor receptor (EGFR) gene fusions comprising the N-terminal of EGFR linked to various fusion partners, most commonly RAD51, are recurrent in lung cancer. We describe five patients with metastatic lung cancer whose tumors harbored EGFR fusions, four of whom were treated with EGFR tyrosine kinase inhibitors (TKI) with documented antitumor responses. In vitro, EGFR–RAD51 fusions are oncogenic and can be therapeutically targeted with available EGFR TKIs and therapeutic antibodies. These results support the dependence of EGFR-rearranged tumors on EGFR-mediated signaling and suggest several therapeutic strategies for patients whose tumors harbor this novel alteration.Significance: We report for the first time the identification and therapeutic targeting of EGFR C-terminal fusions in patients with lung cancer and document responses to the EGFR inhibitor erlotinib in 4 patients whose tumors harbored EGFR fusions. Findings from these studies will be immediately translatable to the clinic, as there are already several approved EGFR inhibitors. Cancer Discov; 6(6); 601–11. ©2016 AACR.See related commentary by Paik, p. 574.This article is highlighted in the In This Issue feature, p. 561