NRG1 Gene Fusions-What Promise Remains Behind These Rare Genetic Alterations? A Comprehensive Review of Biology, Diagnostic Approaches, and Clinical Implications

Non-small cell lung cancer (NSCLC) presents a variety of druggable genetic alterations that revolutionized the treatment approaches. However, identifying new alterations may broaden the group of patients benefitting from such novel treatment options. Recently, the interest focused on the neuregulin-1 gene ( ), whose fusions may have become a potential predictive factor. To date, the occurrence of fusions has been considered a negative prognostic marker in NSCLC treatment; however, many premises remain behind the targetability of signaling pathways affected by the gene. The role of fusions in ErbB-mediated cell proliferation especially seems to be considered as a main target of treatment. Hence, NSCLC patients harboring fusions may benefit from targeted therapies such as pan-HER family inhibitors, which have shown efficacy in previous studies in various cancers, and anti-HER monoclonal antibodies. Considering the increased interest in the gene as a potential clinical target, in the following review, we highlight its biology, as well as the potential clinical implications that were evaluated in clinics or remained under consideration in clinical trials.