Nrg1, or neuregulin-1, is a key physiological ligand to HER3. It contains a receptor-binding epidermal growth factor (EGF)-like domain. NRG1 is involved in activating the ErbB-mediated pathway, which is crucial for various cellular processes such as growth and proliferation [6].

Oncogenic NRG1 fusions, resulting from DNA rearrangements, are rare across different cancer types (<1% incidence), except in invasive mucinous adenocarcinomas (IMAs) of the lung where the incidence of NRG1 fusions can be 10%-30% [1]. NRG1 fusions lead to the activation of downstream growth and proliferation pathways through binding to HER3, heterodimerization with HER2, and activation of the ErbB-mediated pathway [2,4,5,6,7,8,9]. These fusions have been identified in multiple solid tumors including non-small-cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma, and others [1,2,3,5,8,9]. Treatments targeting the ErbB signaling pathway, like afatinib (a pan-ErbB tyrosine kinase inhibitor) and zenocutuzumab (a bispecific antibody against HER2 and HER3), have shown efficacy in patients with NRG1 fusion-positive cancers [1,2,4,5,9].

In conclusion, NRG1 plays a significant role in activating key cellular pathways. The discovery of NRG1 fusions as oncogenic drivers in various solid tumors has led to the development of targeted therapeutic strategies. The study of NRG1 fusions in these cancers helps in understanding the disease mechanisms and provides potential treatment options for patients [1,2,3,4,5,6,7,8,9].