EGFR fusions as novel therapeutic targets in lung cancer

Kartik Konduri, Jean Nicolas Gallant, Young Kwang Chae, Francis J. Giles, Barbara J. Gitlitz, Kyle Gowen, Eiki Ichihara, Taofeek K. Owonikoko, Vijay Peddareddigari, Suresh S. Ramalingam, Satyanarayan K. Reddy, Beth Eaby-Sandy, Tiziana Vavalà, Andrew Whiteley, Heidi Chen, Yingjun Yan, Jonathan H. Sheehan, Jens Meiler, Deborah Morosini, Jeffrey S. RossPhilip J. Stephens, Vincent A. Miller, Siraj M. Ali, Christine M. Lovly

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 languageEnglish
Pages (from-to)601-611
Number of pages11
JournalCancer discovery
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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    Konduri, K., Gallant, J. N., Chae, Y. K., Giles, F. J., Gitlitz, B. J., Gowen, K., Ichihara, E., Owonikoko, T. K., Peddareddigari, V., Ramalingam, S. S., Reddy, S. K., Eaby-Sandy, B., Vavalà, T., Whiteley, A., Chen, H., Yan, Y., Sheehan, J. H., Meiler, J., Morosini, D., ... Lovly, C. M. (2016). EGFR fusions as novel therapeutic targets in lung cancer. Cancer discovery, 6(6), 601-611. https://doi.org/10.1158/2159-8290.CD-16-0075