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NRG1 Fusions: The New Kid on the Block

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Abstract

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.

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Data Availability

No datasets were generated or analysed during the current study.

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Funding

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Author information

Authors and Affiliations

  1. Lombardi Comprehensive Cancer Center, Georgetown University, 3800 Reservoir Road NW, Washington, DC, 20007, USA

    Brinda Gupta & Stephen V. Liu

  2. University of Virginia, Charlottesville, VA, USA

    Leila Borghaei

Authors
  1. Brinda Gupta
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  2. Leila Borghaei
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  3. Stephen V. Liu
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Contributions

All authors wrote the manuscript text. L.B. prepared the original table. All authors reviewed the manuscript.

Corresponding author

Correspondence to Stephen V. Liu.

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Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Conflict of Interest

Brinda Gupta and Leila Borghaei declare no conflict of interest. Stephen V. Liu has received research funding (to institution) from Abbvie, Alkermes, AstraZeneca, Bristol-Myers Squibb, Cogent Biosciences, Duality, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, OSE Immunotherapeutics, Puma, RAPT, Synthekine, and SystImmune; and has received compensation for participation on an advisory board or as a consultant from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Genentech/Roche, Gilead, GSK, Guardant Health, Johnson & Johnson, Jazz Pharmaceuticals, Lilly, Merck, Merus, Mirati, Natera, Novartis, OSE Immunotherapeutics, Pfizer, Regeneron, Revolution Medicines, Takeda, and Yuhan.

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Gupta, B., Borghaei, L. & Liu, S.V. NRG1 Fusions: The New Kid on the Block. Curr Oncol Rep (2025). https://doi.org/10.1007/s11912-025-01640-y

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