Oncogenic Neuregulin 1 gene (NRG1) fusions in cancer: A potential new therapeutic opportunities

It is widely established that chromosomal rearrangements induce oncogenesis in solid tumors. However, discovering chromosomal rearrangements that are targetable and actionable remains a difficulty. Targeting gene fusion or chromosomal rearrangement seems to be a powerful strategy to address malignancies characterized by gene rearrangement. Oncogenic NRG1 fusions are relatively rare drivers that infrequently occur across most tumor types. NRG1 fusions exhibit unique biological properties and are difficult to identify owing to their large intronic regions. NRG1 fusions can be detected using a variety of techniques, including fluorescence in situ hybridization, immunohistochemistry, or next-generation sequencing (NGS), with NGS-based RNA sequencing being the most sensitive. Previous studies have shown that NRG1 fusion protein induces tumorigenesis, and numerous therapies targeting the ErbB signaling pathway, such as ErbB kinase inhibitors and monoclonal antibodies, have initially demonstrated encouraging anticancer efficacy in malignant tumors carrying NRG1 fusions. In this review, we present the characteristics and prevalence of NRG1 fusions in solid tumors. Additionally, we discuss the laboratory approaches for diagnosing NRG1 gene fusions. More importantly, we outline promising strategies for treating malignancies with NRG1 fusion.