HER-2 amplification

P2, N=182, Recruiting, Hebei Medical University Fourth Hospital

However, interpretation is constrained by small retrospective series, assay discordance, and the absence of standardized HER2 scoring criteria for UC. In the antibody-drug conjugate era, resolving these subtype-specific and methodological uncertainties is essential for refining patient selection and defining the clinical role of HER2-directed therapy across histologic subtypes and divergent histologist.

After neoadjuvant oxaliplatin/capecitabine (CAPOX) therapy, he underwent cystoprostatectomy, urethrectomy, and ileal conduit. Pathology showed stage IIIB disease with negative margins. This case underscores a rare but severe complication of prostate brachytherapy, contributing to the clinical understanding of secondary urethral malignancies.

In enrichment analysis, low KIF4A expression is associated with EMT activation, whereas high expression correlates with E2F-mediated proliferation. Although high KIF4A expression suggests an immune-inflamed phenotype, its predictive ability was limited in an independent validation cohort.

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center

BRAF and RAS mutation occurred in 60% and 14% of the patients with available molecular data, respectively. No patients harbored HER2 amplification, suggesting that the co-occurrence of HER2 amplification and dMMR/MSI is essentially anecdotal, making therefore HER2 testing in this subgroup less compelling.

P2, N=30, Not yet recruiting, Sun Yat-sen University

Antibody-drug conjugates (ADCs), led by trastuzumab deruxtecan, have established clinically meaningful activity across multiple solid tumors in HER2 IHC 3+ populations and have further expanded into HER2-low and ultralow expression settings, supporting the concept of HER2 as a biological continuum rather than a binary biomarker...In gastroesophageal adenocarcinoma, treatment options beyond trastuzumab-based regimens continue to diversify: ADC-based standards in later lines are being complemented by next-generation HER2 antibodies, inclu ding recent phase Ⅲ evidence supporting anbenitamab after prior trastuzumab exposure, which may further inform sequencing decisions. Collectively, these advances highlight an emerging precision model in which therapeutic selection and rational sequencing are guided by integrated assessment of HER2 protein expression, ERBB2 genomic status, prior HER2-directed exposure, and toxicity risk (notably ADC-associated interstitial lung disease). Standardization of high-fidelity diagnostic workflows-spanning IHC/ISH quality assurance, re-biopsy when feasible, and context-appropriate use of circulating tumor DNA-will be essential to ensure consistent patient identification and to enable optimal deployment of ADCs, TKIs, and antibody-based therapies across histologic boundaries.

Higher FLOT2 expression in nine HER2 amplified cell lines correlated with a higher T-DM1 IC50 in vitro , and breast cancer patients with high FLOT2 expression had worse survival when receiving either T-DXd (16.2 months (m) vs 18.3 m, p=0.04) or T-DM1 (38.0 m vs 41.3 m, p=0.1) in real-world Caris Life Sciences data. In conclusion, FLOT2 regulates the internalization and cytotoxicity of T-DM1 mediated by Cbl-dependent ubiquitination of HER2. Zoledronic acid disrupts the HER2/FLOT2 interaction, therefore increasing the internalization and cytotoxicity of T-DM1, providing proof of principle that a small molecule inhibitor of the HER2/FLOT2 interaction can enhance the activity of the HER2-targeting ADC.

P1/2, N=36, Recruiting, Beijing Biotech

Metastatic EMPD exhibits distinct clinicopathologic and molecular features, including high AR and HER2 expression, TP53 and CDKN2A/B alterations, and similarity to systemic HER2+ malignancies. The observed activity of HER2-directed therapies in this cohort suggests the potential value of further investigating biomarker-guided treatment strategies in metastatic EMPD. NGS-guided profiling may inform precision treatment strategies, including AR-targeted therapy and emerging MTAP-directed approaches.

Gene expression and DNA methylation data from DAC-treated and untreated T-47D (Luminal-A) and JIMT-1 (HER2-amplified, trastuzumab-resistant with a TNBC-like phenotype) breast cancer cell lines were obtained from a published dataset. Survival analysis identified 114 DAC-responsive genes associated with overall survival in ER/PR-positive BC and 8 in the JIMT-1-derived gene set. DAC induces subtype-dependent epigenomic and transcriptional remodeling, selectively disrupts age-associated regulatory programs, and underscores the need for subtype-stratified evaluation of epigenetic therapies in breast cancer.