HER-2 amplification

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.

Although HER2-targeted therapies, such as trastuzumab deruxtecan, have shown promising results in HER2-positive bladder cancer, optimal immunohistochemistry (IHC) scoring criteria for urothelial carcinoma remain unclear...Upper GI and breast scoring criteria yield divergent scores in a significant subset of urothelial carcinomas, potentially affecting eligibility for targeted therapy. Associations with histologic subtype and metastatic site support disease-specific diagnostic and therapeutic strategies.

The past two decades have witnessed transformative advances in HER2-targeted therapeutics, exemplified by tyrosine kinase inhibitors (TKIs), including first-generation reversible pan-HER (e.g., lapatinib), second-generation covalent pan-HER (neratinib, pyrotinib), and novel selective HER2 inhibitors (tucatinib, sevabertinib, zongertinib). This review comprehensively summarizes recent advances in HER2-targeted TKIs and their emergent resistance mechanisms, further analyzing strategies to both mitigate off-target toxicity and overcome resistance through rational design of selective HER2 inhibitors. Collectively, these insights provide a roadmap for developing next-generation precision therapies in HER2-driven cancers.

The patient underwent radical nephrectomy followed by biomarker-guided FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy combined with camrelizumab immunotherapy, achieving a progression-free survival of approximately 7 months, accompanied by a temporary decline in tumor markers. Therapeutically, while the identified biomarker provided a rationale for precision therapy, the resulting clinical benefit was limited and transient. This suggests that the aggressive biology and spatial heterogeneity typical of CUP can attenuate the long-term efficacy of biomarker-guided interventions.

The study also demonstrates how genetic changes, metabolism, and epigenetics work in concert with sex hormones to modulate breast cancer development. SERMs, aromatase inhibitors, and the endocrine approach are described, as well as novel directions to develop inhibitors of androgen and other hormone signaling pathways.

Finally, we discussed the translational challenges and propose solutions for developing PTM-based diagnostics and therapies for TNBC. An evidence stratification framework was applied to grade the strength of the reviewed findings, distinguishing mechanistically validated, correlative, and clinically actionable evidence.

In this nationwide metastatic cohort, FGFR3 alterations and ERBB2 amplification were each detected in approximately 15% of cases and showed a significant but partial negative association. These findings clarify the molecular epidemiology of mUC and support comprehensive genomic profiling to guide biomarker-driven therapy.

Importantly, hsa-miR-27b-5p upregulation independently predicted worse overall survival, whereas hsa-miR-128-3p upregulation independently predicted improved survival outcomes. These findings identify distinct microRNA signatures associated with HER2 pathway alterations and prognosis in gastric cancer, highlighting their potential as biomarkers and contributors to HER2-driven tumor biology.

EGFR tyrosine kinase inhibitors (TKIs) have transformed management, with first-line osimertinib demonstrating a median progression-free survival (PFS) of 18.9 months and overall survival (OS) of 38.6 months in the FLAURA trial...Understanding these mechanisms is critical for optimizing patient outcomes and guiding personalized therapeutic approaches. This review discusses current strategies to delay or overcome resistance and highlights emerging therapeutic avenues with the potential to reshape the management of EGFR-mutant NSCLC.

These findings highlight the evolving nature of HER2 testing in EC and demonstrate the significant impact of scoring methodology on HER2 interpretation. Our results support the development of EC-specific HER2 testing guidelines and a dual-reporting approach incorporating both ISGyP and gastric scoring criteria, with selective confirmatory FISH testing, to optimize patient selection for HER2-targeted therapies.

These observed frequencies should be interpreted as case-level implementation signals surfaced through routine CGP rather than assay superiority evidence, biological prevalence estimates, or treatment-benefit data. This nationwide, platform-aware benchmark supports practical interpretation of tumor-agnostic eligibility signals in routine CGP practice in Japan.

P3, N=360, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended