NRG1 fusions：The potential targeted treatment in non-small cell lung cancer(NSCLC)

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Neuregulin 1 (NRG1) gene fusions are rare but actionable oncogenic drivers in non-small cell lung cancer (NSCLC).
• Understanding the molecular mechanisms and therapeutic targets for NRG1 fusion-positive NSCLC is crucial for advancing precision oncology.

Purpose of the Study:

• To review recent advances in targeted therapies for NRG1 fusion-positive NSCLC.
• To focus on molecular mechanisms, diagnostic methods, and clinical evidence for emerging treatments.
• To identify challenges and unmet needs in managing this NSCLC subset.

Main Methods:

• Literature review synthesizing recent research on NRG1 fusion-positive NSCLC.
• Analysis of clinical data for HER3-directed monoclonal antibodies, pan-HER TKIs, HER2-selective TKIs, and bispecific antibodies.
• Examination of resistance mechanisms, including NRG1 fusion isoform heterogeneity and EGFR pathway activation.

Main Results:

• HER3-targeted agents demonstrated partial responses in 35-40% of patients.
• Median progression-free survival ranged from 4.6 to 6.2 months with HER3-targeted therapies.
• Intrinsic resistance due to fusion heterogeneity and EGFR pathway activation presents a significant challenge.

Conclusions:

• Targeted therapies, particularly HER3-directed agents, offer therapeutic potential for NRG1 fusion-positive NSCLC.
• Addressing resistance mechanisms and standardizing diagnostic protocols are essential for optimizing treatment outcomes.
• Further development of novel therapeutics and collaborative clinical trials are necessary for this molecularly defined NSCLC population.