HER-2 positive + HER-2 overexpression

Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based classifications to combined morphological and molecular approaches, with therapeutic implications, is also addressed.

These findings indicate that metformin synergistically enhances the antitumor activity of alpelisib in HER2-positive breast cancer by inhibiting oncogenic signaling and stemness pathways. Beyond its metabolic benefit in mitigating hyperglycemia, metformin may potentiate PI3K-targeted therapies, supporting further preclinical and clinical evaluation of this combination strategy.

Trastuzumab-based therapy has shown survival benefit in HER2-positive SEC, leading to its inclusion in current treatment guidelines...The prognostic value remains debated, though recent trials of antibody-drug conjugates (e.g., T-DXd) show promise...Diagnostic challenges include variable scoring systems, intratumoral heterogeneity, and HER2-low classification. Standardization of testing criteria and further clinical validation of HER2-targeted strategies across gynecologic tumors are essential to guide personalized therapy and improve outcomes.

P2, N=33, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=185 --> 33 | Trial completion date: Feb 2026 --> Dec 2024 | Recruiting --> Terminated; Abandon of the partner, ROCHE

Temporal analysis showed conversion rates of 50.0% for synchronous metastases, 30.8% within 12 months, and 63.6% beyond 12 months. We identified a high prevalence of HER2-low and HER2-ultralow subtypes, suggesting potential eligibility for ADC therapies.

This study identifies a significant association between HER2 overexpression and lymph node metastasis in gastric cancer, suggesting HER2 expression is associated with more advanced lymph node involvement in this cohort; no significant association with overall survival was observed (log-rank p=0.58), though its impact on survival remains inconclusive.

In summary, this study highlights the critical role of CAND1 in regulating HER2 ubiquitination and suggests a potential therapeutic strategy for patients with HER2-positive breast cancer.

CELF1 promotes aerobic glycolysis and aggressive behavior in ER-positive breast cancer, at least partly by regulating GLUT1. These findings reveal RBP-driven metabolic reprogramming in luminal A disease and nominate the CELF1-GLUT1 axis as a potential therapeutic vulnerability.

She received carboplatin/paclitaxel plus avelumab, followed by pegylated liposomal doxorubicin and weekly paclitaxel. This case illustrates that T-DXd can induce deep and durable remission in HER2-positive, dMMR metastatic serous endometrial cancer after multiple lines of therapy. It adds real-world evidence supporting further investigation of HER2-directed antibody-drug conjugates in gynaecologic malignancies, and underscores the need for confirmatory trials and refined biomarker-driven patient selection.

P2, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026

The patient subsequently received trastuzumab combined with low-dose nab-paclitaxel, achieving a partial response according to RECIST 1.1 criteria. At the most recent follow-up, the patient remains in stable condition. This case highlights the efficacy and safety of HER2-targeted combination therapy in elderly SDC patients, offering valuable insights into biomarker-driven personalized treatment strategies for this population.

HER2 expression is closely associated with meningioma pathogenesis and grade. This highlights HER2 as a potential biomarker and therapeutic target, warranting further clinical trials to explore HER2-targeted therapies, such as trastuzumab, for aggressive and non-resectable meningiomas.