TY - JOUR
T1 - EGFR fusions as novel therapeutic targets in lung cancer
AU - Konduri, Kartik
AU - Gallant, Jean Nicolas
AU - Chae, Young Kwang
AU - Giles, Francis J.
AU - Gitlitz, Barbara J.
AU - Gowen, Kyle
AU - Ichihara, Eiki
AU - Owonikoko, Taofeek K.
AU - Peddareddigari, Vijay
AU - Ramalingam, Suresh S.
AU - Reddy, Satyanarayan K.
AU - Eaby-Sandy, Beth
AU - Vavalà, Tiziana
AU - Whiteley, Andrew
AU - Chen, Heidi
AU - Yan, Yingjun
AU - Sheehan, Jonathan H.
AU - Meiler, Jens
AU - Morosini, Deborah
AU - Ross, Jeffrey S.
AU - Stephens, Philip J.
AU - Miller, Vincent A.
AU - Ali, Siraj M.
AU - Lovly, Christine M.
N1 - Funding Information:
The authors thank the patients and their families. They are grateful to William Pao and Catherine Meador for critical review of the manuscript. Grant Support This study was supported in part by the NIH and NCI R01CA121210 (C.M. Lovly) and P01CA129243. Research was supported by the 2015 AACR-Genentech BioOncology Career Development Award for Cancer Research on the HER Family Pathway, grant number 15-2018-LOVL (to C.M. Lovly). C.M. Lovly, J.-N. Gallant, and J.H. Sheehan were supported by a V Foundation Scholar-in-Training Award. C.M. Lovly was additionally supported by a Damon Runyon Clinical Investigator Award and a LUNGevity Career Development Award. J.-N. Gallant was additionally supported by F30CA206339 and MSTP grant T32GM007347. Work in the Meiler laboratory is supported through the NIH (R01GM080403, R01GM099842, R01DK097376, R01HL122010, and R01GM073151) and the NSF (CHE1305874). T. Vaval? and B.J. Gitlitz were part of the Genomic of Young Lung Cancer study (GoYLC; NCT02273336), which was funded by the Bonnie J. Addario Lung Cancer Foundation, the Peter Barker Foundation, Genentech, the Beth Longwell Foundation, the Schmidt Legacy Foundation, and Upstage Lung Cancer.
Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/6
Y1 - 2016/6
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85011990388&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011990388&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-16-0075
DO - 10.1158/2159-8290.CD-16-0075
M3 - Article
C2 - 27102076
AN - SCOPUS:85011990388
VL - 6
SP - 601
EP - 611
JO - Cancer Discovery
JF - Cancer Discovery
SN - 2159-8274
IS - 6
ER -
