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NRG1 Fusion — SCE Medical Oncology MCQ

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HardLung CancerNRG1 FusionSCE Medical Oncology

RNA sequencing in an invasive mucinous lung adenocarcinoma identifies a functional NRG1 fusion. Which biological rationale supports referral for a molecular trial or access programme using zenocutuzumab?

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Correct answer: B — NRG1-driven HER2-HER3 heterodimer signalling is targetable with a bispecific antibody

NRG1 fusion proteins activate HER3 and promote HER2-HER3 heterodimers, which zenocutuzumab blocks through dual HER2/HER3 binding. NRG1-driven HER2-HER3 signalling is targetable with a selective HER3 kinase inhibitor: HER3 lacks conventional kinase activity and zenocutuzumab is a bispecific antibody. NRG1-driven EGFR-HER3 signalling is targetable with a bispecific antibody: the defining oncogenic heterodimer partner targeted by zenocutuzumab is HER2. NRG1-driven HER2-HER4 signalling is targetable with a bispecific antibody: NRG1 chiefly activates HER3 in this fusion context. NRG1-driven FGFR2-FGFR3 signalling is targetable with a bispecific antibody: FGFR signalling is not the NRG1-fusion dependency.

Reference: Efficacy of zenocutuzumab in NRG1-fusion-positive cancer (Published February 2025): https://pubmed.ncbi.nlm.nih.gov/39908431/; NICE NG122 lung cancer: recommendations (Current NICE recommendations, accessed July 2026): https://www.nice.org.uk/guidance/ng122/chapter/Recommendations