Ampulla of Vater Carcinoma

This study identifies NKG2A-HLA-E and TIM3-galectin 9 pathways as key mechanisms in PDAC progression and immune inhibition and provides a mechanistic rationale for combining their blockade with PD-1-PD-L1 blockade as a potential therapeutic strategy.

Our study presents a single-cell atlas of AoV carcinoma, highlighting the molecular diversity of malignant epithelium and its association with the immune microenvironment. The PB-KRAS subtype emerges as a stem-like, immunosuppressive tumor state associated with poor prognosis, providing insights for future therapeutic targeting.

MUC16 knockout markedly reversed EMT, attenuated invasive and migratory capacities, and restored chemosensitivity in both cell lines and their xenograft models. Collectively, our findings establish AMS as a prognostically and therapeutically informative molecular classification framework for AMPAC, unveil the critical role of the tumor microenvironment in AMPAC heterogeneity, and provide a translational foundation for precision oncology in this rare tumor.

These findings demonstrate that MET dysregulation is a recurrent molecular event in ampullary carcinoma and support further investigation of MET and HER2 co-expression as a basis for future mechanistic and therapeutic studies.

Sequential systemic chemotherapy including durvalumab is suggested as a useful future treatment option and may contribute to conversion surgery for unresectable ampulla of Vater carcinoma.

P=N/A, N=170, Recruiting, Insel Gruppe AG, University Hospital Bern | Trial completion date: Jul 2029 --> Oct 2030 | Trial primary completion date: Jul 2029 --> Oct 2030

P=N/A, N=36, Recruiting, Dartmouth-Hitchcock Medical Center | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Sep 2026 --> Sep 2027

P2, N=54, Recruiting, Yale University | Initiation date: Mar 2026 --> Jun 2026

Epigenetic dysregulation and recent applications of single-cell and spatial transcriptomics highlighted tumour heterogeneity. Despite progress, evidence remains uneven across cancer types, with limited exploration of germline variants beyond colorectal, pancreatic, and select liver cancers.

Subgroup analyses revealed no significant differences in miRNA expression across histological subtypes or tumor stages. Serum miR‑199 and miR‑19 showed exploratory concordance between circulating and tumor tissue expression in PACA, but their clinical utility remains limited and requires validation in a larger cohort.

P=N/A, N=845, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University | Recruiting --> Active, not recruiting | Trial completion date: Apr 2026 --> May 2031 | Trial primary completion date: Apr 2026 --> Aug 2028

The benefit-cost ratio (BCR) analysis demonstrated the greater cost-effectiveness of genetic testing compared to endoscopic surveillance to all relatives at risk. Although our cohort is clinically enriched and does not reflect the population prevalence of LS in Southern Thailand, these findings highlight the substantial LS burden within high-risk families and underscore the importance of incorporating genetic screening, counseling, and tailored surveillance strategies into clinical practice.