HER-2 positive + HER-2 overexpression

P1/2, N=52, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Apr 2025 --> Sep 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

As a novel survival biomarker in gastric cancer, HER2 overexpression indicates unfavorable prognosis among both resectable and advanced patients, irrespective of East Asian or non-East Asian populations. PROSPERO (CRD42020168051).

We concluded that HER2 signals through the RIP signaling pathway that promotes cell proliferation and is targeted by trastuzumab. The aberrant HER2 RIP signaling confers resistance to trastuzumab that could be overcome by the application of inhibitors to ADAM10 and γ-secretase.

Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.

This study revealed the incidence and clinical outcomes of HER2-low expression in de novo advanced breast cancer, suggesting favorable outcomes, particularly in HR-positive breast cancer. These findings may inform personalized treatment strategies. Further research into the mechanisms and implications of HER2-low expression in breast cancer is required.

We found that patients with HER2-high disease were more likely to achieve pCR after NAT compared to patients with HER2-intermediate BC, a subgroup of patients that may benefit from more personalized NAT strategies.

Our study highlights the variable expression and significance of HER2 testing across multiple solid tumor types, reinforcing the importance of HER2 testing to optimize the utilization of T-Dxd in the real-world setting.

Although p53abn ECs are clinically aggressive, these tumours may present different molecular features as HER2 overexpression/amplification. Anti-HER2 target therapy represents a new therapeutic option. HER2-positive carcinomas represent a subgroup of tumours characterized by distinct histological features, although without significant prognostic impact.