The role of NRG1 and its receptor HER3 in gastrointestinal tumors

Abstract

Neuregulin 1 (NRG1), as a key ligand of the epidermal growth factor receptor family, plays a crucial role in the initiation, progression, and metastasis of various solid tumors by binding to human epidermal growth factor receptor 3 (HER3) and activating downstream signaling pathways. In recent years, NRG1 gene fusions have been identified as rare oncogenic drivers in gastrointestinal tumors, with their abnormal expression in gastric and colorectal cancers closely associated with poor patient prognosis. This paper systematically reviews the biological functions and mechanisms of the NRG1/HER3 signaling axis in gastrointestinal tumors, while outlining research progress on its potential as a therapeutic target. Given the rapid development and exploratory nature of this field, this narrative review synthesizes key biological discoveries and clinical advances from current literature. It further explores the clinical prospects and challenges of therapeutic strategies targeting the NRG1/HER3 pathway, including treatment efficacy heterogeneity, complex mechanisms of drug resistance, and clinical limitations of different targeted agents. This review aims to provide a theoretical reference for subsequent research and clinical practice.