HER-2 (Human epidermal growth factor receptor 2)

P2, N=100, Recruiting, Jeeyun Lee | N=50 --> 100

With this technology, we developed trastuzumab deruxtecan, the first DXd-ADC directed toward HER2. Additionally, Dato-DXd showed TROP2-dependent antitumor activity in multiple human cancer cell line-derived and patient-derived xenograft mouse models. Clinically, the global phase III trial targeting hormone receptor-positive, HER2-negative, unresectable or recurrent breast cancer led to its first approval in Japan in December 2024, followed by the approvals in the US and Europe later.

In contrast, TROP2-directed ADCs demonstrate negligible cardiac signals. Given the elevated fatality rate of serious cardiac events associated with T-DXd observed in real-world data, we propose a risk-stratified cardiac monitoring algorithm incorporating high-sensitivity troponin and global longitudinal strain for patients receiving next-generation ADCs.

Present findings are from a small sample cohort and need further validation from a larger cohort. The online version contains supplementary material available at 10.1007/s13193-025-02427-0.

Moreover, this "Breast HERV19" expression signature was associated with better prognosis in HR+HER2- eBC, in which its expression was also correlated with biomarkers of sensitivity to anti PD-1 immunotherapy, such as tumor-infiltrating lymphocytes (TILs), PD-L1, and estrogen receptor (ER) expression levels. In eBC, our "Breast HERV19" expression signature makes it possible to isolate a subgroup of HR+HER2- tumors presenting strong immunogenicity, better prognosis, and biological characteristics that suggest a possible benefit from immunotherapy.

The calibration curves indicated good agreement and DCA confirmed the clinical utility of the model. The proposed nomogram demonstrated robust predictive performance for patients with breast cancer and liver metastases and may provide valuable prognostic information, pending further validation.

Adjuvant ADC+ICI showed comparable short-term OS and directionally favorable DFS/PFS trends versus GC, with a distinct toxicity profile. These findings are hypothesis-generating and require prospective validation.

The anti-Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) monoclonal antibody ramucirumab was the first antiangiogenic agent approved for HER2-negative metastatic gastric adenocarcinomas and remains a standard second-line treatment either alone or in combination with paclitaxel. Other VEGFR-targeting agents, such as the tyrosine kinase inhibitors (TKI) regorafenib and apatinib, have failed to demonstrate any survival benefit in the first-line settings, while providing modest improvements in pretreated patients, even when combined with Immune Checkpoint Inhibitors (ICI)...Although several biomarker candidates have been explored, reliable predictors are still awaited. This review summarizes current evidence and explores the future of antiangiogenic agents in gastric cancers.

Particular attention is given to HER2-directed antibody-drug conjugates, especially trastuzumab deruxtecan (T-DXd), which have emerged as an important recent therapeutic advance and have renewed interest in HER2 as an actionable target in selected patients with HER2-expressing cervical carcinoma. This review further highlights the need for biomarker-driven patient selection, standardized HER2 assessment, and rational integration of HER2-directed strategies into precision treatment for CC.

Nationwide real-world data demonstrate favorable survival outcomes following adoption of dual anti-HER2 therapy. While these findings are broadly consistent with the CLEOPATRA trial, the observational design does not allow direct assessment of equivalence between studies.

These underscore the relevance of age-related biological factors in shaping breast cancer characteristics. However, among Indonesian women over 45 years old, the proportion of high breast density remains remarkably high (65.6%), suggesting that factors beyond age-such as genetic, hormonal, or lifestyle influences-may contribute to the persistence of dense breast tissue in this population.

This approach offers a promising, non-invasive alternative to traditional tissue sampling by enabling a "digital biopsy." Integrating these models into clinical workflows could reduce the diagnostic burden on patients and facilitate personalized treatment planning. However, further validation in larger, prospective cohorts is necessary.