HER-2 amplification

Compared with amplification, oncogenic ERBB2 mutations are preferentially associated with higher TMB/MSI-H and characteristic co-mutation signatures, supporting the clinical evaluation of mutation-selective HER2 inhibitors and rational combinations with immune checkpoint blockade. Our findings expand the molecular epidemiology of ERBB2 in Chinese GI cohorts, suggesting potential implications for resistance to standard chemotherapy or anti-EGFR strategies in select settings.

P1/2, N=18, Active, not recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Apr 2026 --> Apr 2027 | Recruiting --> Active, not recruiting

P2, N=42, Recruiting, Gruppo Oncologico del Nord-Ovest

P3, N=3380, Not yet recruiting, UNICANCER

P1, N=165, Recruiting, Iksuda Therapeutics Ltd. | Trial completion date: Sep 2027 --> Dec 2027 | Trial primary completion date: Sep 2026 --> Dec 2026

P1, N=30, Recruiting, Vanderbilt-Ingram Cancer Center | Not yet recruiting --> Recruiting

© 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Stratified analysis revealed that unequivocal cases (Groups 1 + 5, approximately 84% of the cohort) maintained excellent concordance (coefficient of variation <5%) at all tiers, while equivocal cases (Groups 2-4) exhibited persistently higher variability regardless of cell count. These findings validate the 20-cell minimum for routine FISH-based HER2 assessment and demonstrate that enhanced concordance in borderline cases requires adjudicatory workflows beyond additional cell counting.

P1/2, N=129, Not yet recruiting, Medica Scientia Innovation Research S.L.

We present a case of a 66-year-old female with de novo metastatic NSCLC harboring an EGFR mutation, RET rearrangement, and ERBB2 amplification, who experienced transformation to SCLC while on osimertinib. Subsequently, she exhibited primary refractory disease to both first-line platinum doublet with immunotherapy and second-line lurbinectedin...The patient had minimal side effects and obtained a partial response with a progression-free survival (PFS) of 13.1 months, better than historically poor prognosis seen in transformed SCLC. This case underscores the potential role of human epidermal growth factor receptor 2 (HER-2) directed therapies, such as T-DXd, in transformed SCLC.

In summary, our study establishes the comprehensive molecular atlas and a targeted therapeutic subtyping framework, revealing therapeutic vulnerabilities and providing novel insights for advancing precision oncology in OCCC management.

Integrated genomic and transcriptomic profiling refines prognostic stratification in cholangiocarcinoma independent of therapeutic actionability. KRAS-TP53 co-mutation and the Mesenchymal transcriptomic subtype represent independent high-risk markers detectable on routine FFPE tissue. These features complement actionable alterations and may inform patient selection and clinical trial design.