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Purpose of Review <p>Neuregulin 1 (<i>NRG1)</i> fusions are rare but actionable oncogenic drivers that occur in a variety of tumor types, including non-small cell lung cancer (NSCLC). These fusions lead to pathophysiologic activation of HER signaling pathways, promoting tumor growth, invasion, and metastasis. Current evidence suggests that <i>NRG1</i> fusion-positive NSCLC does not respond well to conventional treatments such as immunotherapy and chemotherapy. This review focuses on the biology and detection of <i>NRG1</i> fusions and the evolving therapeutic landscape of NSCLC harboring <i>NRG1</i> fusions.</p> Recent Findings <p>Zenocutuzumab, a bispecific antibody targeting HER2 and HER3, is the first FDA approved treatment for previously treated <i>NRG1</i> fusion-positive NSCLC and pancreatic cancer. Additional <i>NRG1</i> fusion directed strategies are in development.</p> Summary <p><i>NRG1</i> fusions are rare molecular drivers of NSCLC that can be effectively treated with targeted therapies. Here, we summarize the biology and detection of <i>NRG1</i> fusions, the currently approved bispecific antibody used to treat <i>NRG1</i> fusion-positive NSCLC, and new agents under investigation.</p>

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NRG1 Fusions: The New Kid on the Block

  • 期刊论文

  • 发表日期：

    2025年1月31日

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  • Brinda Gupta,
  • Leila Borghaei,
  • Stephen V. Liu

摘要

Purpose of Review

Neuregulin 1 (NRG1) fusions are rare but actionable oncogenic drivers that occur in a variety of tumor types, including non-small cell lung cancer (NSCLC). These fusions lead to pathophysiologic activation of HER signaling pathways, promoting tumor growth, invasion, and metastasis. Current evidence suggests that NRG1 fusion-positive NSCLC does not respond well to conventional treatments such as immunotherapy and chemotherapy. This review focuses on the biology and detection of NRG1 fusions and the evolving therapeutic landscape of NSCLC harboring NRG1 fusions.

Recent Findings

Zenocutuzumab, a bispecific antibody targeting HER2 and HER3, is the first FDA approved treatment for previously treated NRG1 fusion-positive NSCLC and pancreatic cancer. Additional NRG1 fusion directed strategies are in development.

Summary

NRG1 fusions are rare molecular drivers of NSCLC that can be effectively treated with targeted therapies. Here, we summarize the biology and detection of NRG1 fusions, the currently approved bispecific antibody used to treat NRG1 fusion-positive NSCLC, and new agents under investigation.