Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors

Abstract

The fusion genes NRG1 and NRG2, members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1-positive patients. Currently, there are no approved targeted drugs for NRG1 and NRG2. Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.

Keywords

tyrosine receptor kinase / monoclonal antibodies / precision medicine / targeted therapy / solid tumor / fusion

Authors' Contributions

J.C. and Z.S. participated in the design of the expert consensus. C.X., Q.W., D.W., W.W., and W.F. conceived of the expert consensus and participated in its design and other authors coordination and helped to draft the expert consensus. All authors read and approved the final manuscript.

Funding

This work was supported by the Natural Science Foundation of China (grant numbers 82002456), China Postdoctoral Science Foundation (grant numbers 2022M723207), the Medical Scientific Research Foundation of Zhejiang Province of China (grant numbers 2023KY666), Zhejiang Traditional Chinese Medicine Science Fund Project (grant numbers 2024ZL372), Qiantang Cross Fund Project (grant numbers 2023-16), National Natural Science Foundation of China of Zhejiang Cancer Hospital Cultivation Project (grant numbers PY2023006), the Medical Scientific Research Foundation of Zhejiang Province of China (grant numbers 2024KY812), and The Natural Science Foundation of Zhejiang Province (grant numbers Q24H160110).

Conflict of Interest

None declared.

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