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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• NRG1 and NRG2 fusions, part of the epidermal growth factor (EGF) receptor family, are increasingly recognized as critical oncogenic drivers.
• These fusions promote uncontrolled cell proliferation by retaining the EGF-like active domain, leading to aberrant signaling through the ERBB ligand family.

Purpose of the Study:

• To review the current understanding of NRG1 and NRG2 gene fusions in solid tumors.
• To discuss diagnostic strategies and therapeutic approaches for cancers harboring these fusions.
• To propose a consensus for expert diagnosis and treatment, highlighting the role of clinical trials.

Main Methods:

• Literature review of studies on NRG1 and NRG2 gene fusions.
• Analysis of incidence rates across various cancer types, with a focus on lung cancer.
• Evaluation of diagnostic techniques including RNA-based next-generation sequencing and pERBB3 immunohistochemistry.
• Review of current and emerging therapeutic strategies, including pan-ERBB inhibitors and targeted agents.

Main Results:

• NRG1 gene fusions occur in 0.19–0.27% of lung cancers, with CD74 and SLC3A2 as common fusion partners.
• RNA-based next-generation sequencing is the primary detection method; pERBB3 immunohistochemistry can be used for prescreening.
• No drugs are currently approved specifically for NRG1/NRG2 fusions, but various ERBB-targeting therapies are employed.
• Clinical trials are essential for advancing treatment for patients with these specific genetic alterations.

Conclusions:

• NRG1 and NRG2 gene fusions represent significant oncogenic drivers requiring precise diagnostic and therapeutic strategies.
• A multidisciplinary consensus is needed to optimize patient management.
• Further research and clinical trials are imperative to develop effective targeted treatments and improve outcomes for patients with NRG1/NRG2 fusion-positive solid tumors.