EGFR Fusions as Novel Therapeutic Targets in Lung Cancer.

Konduri K, Gallant JN, Chae YK, Giles FJ, Gitlitz BJ, Gowen K, Ichihara E, Owonikoko TK, Peddareddigari V, Ramalingam SS, Reddy SK, Eaby-Sandy B, Vavalà T, Whiteley A, Chen H, Yan Y, Sheehan JH, Meiler J, Morosini D, Ross JS, Stephens PJ, Miller VA, Ali SM, Lovly CM
Cancer Discov. 2016 6 (6): 601-11

PMID: 27102076 · PMCID: PMC4893907 · DOI:10.1158/2159-8290.CD-16-0075

UNLABELLED - 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. 574This article is highlighted in the In This Issue feature, p. 561.

©2016 American Association for Cancer Research.

MeSH Terms (24)

Adult Antineoplastic Agents Biomarkers Cell Line, Tumor Combined Modality Therapy ErbB Receptors Exons Female Genetic Loci High-Throughput Nucleotide Sequencing Humans Introns Lung Neoplasms Magnetic Resonance Imaging Male Middle Aged Models, Molecular Molecular Targeted Therapy Neoplasm Metastasis Oncogene Proteins, Fusion Protein Conformation Protein Kinase Inhibitors Rad51 Recombinase Young Adult

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