NRG1 Fusions in Solid Tumors


Brinda Gupta, Sharon Wu, Sai-Hong Ou, Sourat Darabi, Kathryn Mileham, Nishant Gandhi, Benjamin Weinberg, Misako Nagasaka, Hossein Borghaei, Patrick Ma, Alex Farrell, George Sledge, Ari Vanderwalde, Wafik El-Deiry, Stephen Liu


  • NRG1 gene fusions are rare but actionable genomic drivers that occur across a growing number of tumor types.
  • NRG1 has an EGF-like domain that serves as a ligand for ErbB (HER3) receptors, thereby inducing heterodimerization, usually with HER2, and subsequent activation of relevant downstream signaling pathways.
  • Agents targeting the HER2/HER3 pathway have shown early clinical promise in NRG1 fusion-positive cancers.
  • The HER2/HER3 bispecific antibody zenocutuzumab has FDA Fast Track Designation for tumors with NRG1 fusions.


  • NRG1 fusions are rare but actionable genomic events that occur across many tumor types.
  • There are a wide variety of fusion partners within and across tumor types.
  • The clinical implications of the heterogeneity among fusion partners warrants further investigation.
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