RT Journal Article
SR Electronic
T1 <em>EGFR</em> 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