NCI-H2170-ERBB2-YVMA-KI cell line

Human epidermal growth factor receptor 2 (HER2, encoded by ERBB2) exon 20 insertions are recognized as oncogenic drivers in a subset of non‑small cell lung cancer (NSCLC). Among these, the in‑frame insertion A775_G776insYVMA (p.A771_Y772insYVMA, also referred to as HER2‑YVMA) is the most prevalent alteration, accounting for approximately 70–83% of all HER2 exon 20 insertions, particularly in lung adenocarcinoma. This mutation occurs predominantly in younger, never‑ or light‑smoking female patients with adenocarcinoma histology.
The YVMA insertion introduces structural changes in the HER2 kinase domain, alters the secondary structure of the loop region, and creates steric hindrance that reduces the binding affinity of conventional HER2‑targeted tyrosine kinase inhibitors (TKIs) such as afatinib, while conferring partial sensitivity to newer agents like pyrotinib and poziotinib. Compared with non‑exon 20 HER2 alterations, tumors harboring exon 20 insertions exhibit a higher risk of metastasis (including brain metastases, which occur in ~50% of patients) and poorer prognosis, with chemotherapy historically showing limited efficacy. Recent advances have introduced novel HER2‑directed antibody–drug conjugates (e.g., trastuzumab deruxtecan) and more selective TKIs (zongertinib, sevabertinib), which are reshaping the treatment paradigm for this molecular subset.