NRG1 Fusions in NSCLC: Being eNRGy Conscious.

Abstract

Fusions in neuregulin 1 (NRG1) are rare oncogenic drivers that occur across a number of tumor types, including non-small cell lung cancer (NSCLC). NRG1 has an EGF-like domain that serves as a ligand for HER3 receptors, inducing heterodimerization, usually with HER2, and subsequent activation of oncogenic downstream signaling pathways. Emerging evidence suggests that NSCLC harboring NRG1 fusions do not respond as well to standard therapeutic options including chemotherapy and immunotherapy, and prognosis is poor. Novel treatment approaches targeting the HER2/HER3 pathway are under investigation. Here, we discuss the biology and detection of NRG1 fusions in NSCLC and promising targeted treatment strategies for tumors harboring the mutation.