NRG1融合：非小細胞肺癌（NSCLC）における潜在的な標的治療

Neuregulin 1 (NRG1) gene fusions represent a rare but clinically actionable oncogenic driver in non-small cell lung cancer (NSCLC). This review synthesizes recent advances in targeted therapies for NRG1 fusion-positive NSCLC, with a focus on the underlying molecular mechanisms, diagnostic methodologies, and emerging clinical evidence. Current evidence demonstrates the therapeutic potential of various approaches, including HER3-directed monoclonal antibodies, pan-HER tyrosine kinase inhibitors (TKIs), HER2-selective TKIs, and novel bispecific antibodies. Clinical data have reported partial responses in approximately 35-40% of patients treated with HER3-targeted agents, accompanied by a median progression-free survival ranging from 4.6 to 6.2 months. Critical challenges persist, such as intrinsic resistance mediated by the heterogeneity of NRG1 fusion isoforms and compensatory activation of the epidermal growth factor receptor (EGFR) pathway. This comprehensive analysis underscores the unmet need for novel therapeutics and provides a framework for optimizing precision oncology strategies in this molecularly defined NSCLC subset, highlighting the necessity for standardized diagnostic protocols and globally collaborative clinical trials.