Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 601-611 |
| Number of pages | 11 |
| Journal | Cancer Discovery |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
Cite this
EGFR fusions as novel therapeutic targets in lung cancer. / Konduri, Kartik; Gallant, Jean Nicolas; Chae, Young Kwang; Giles, Francis J.; Gitlitz, Barbara J.; Gowen, Kyle; Ichihara, Eiki; Owonikoko, Taofeek K.; Peddareddigari, Vijay; Ramalingam, Suresh S.; Reddy, Satyanarayan K.; Eaby-Sandy, Beth; Vavalà, Tiziana; Whiteley, Andrew; Chen, Heidi; Yan, Yingjun; Sheehan, Jonathan H.; Meiler, Jens; Morosini, Deborah; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.; Ali, Siraj M.; Lovly, Christine M.
In: Cancer Discovery, Vol. 6, No. 6, 01.06.2016, p. 601-611.Research output: Contribution to journal › Article
}
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.
PY - 2016/6/1
Y1 - 2016/6/1
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
VL - 6
SP - 601
EP - 611
JO - Cancer Discovery
JF - Cancer Discovery
SN - 2159-8274
IS - 6
ER -