Neuroendocrine prostate cancer (NEPC) is an aggressive, treatment-refractory phenotype of advanced prostate cancer. This narrative review was informed by targeted searches of PubMed, Web of Science through May 2026. We classify evidence as Level A (human NEPC samples or clinical cohorts), Level B (NEPC-specific models), Level C (prostate adenocarcinoma or CRPC without NEPC resolution), or Level D (pan-cancer or non-prostate extrapolation), and apply these levels to central claims and a study-level evidence table. Direct human data support immune depletion in most NEPC tumors, with heterogeneous macrophage, fibroblast and lymphoid remodeling in selected cohorts; model studies support context-dependent cytokine, hypoxic, extracellular-matrix and metabolic effects on lineage plasticity. By contrast, CAF-derived lactate fueling NEPC, a dense collagen drug barrier, and NEPC-specific vascular permeability remain unvalidated. Most TME-directed treatments are preclinical or extrapolated, whereas DLL3-directed therapy has shown early activity in biomarker-selected disease. Longitudinal biopsies, spatial multi-omics, humanized models and biomarker-defined trials are needed to distinguish causal vulnerabilities from correlates of treatment-emergent lineage transition.
Nan Yao, Qi-Xing Yang, Peng-Kang Chang et al.· Frontiers in Oncology· 0 citations
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) represents a highly lethal malignancy. The FOXA2 was involved in cellular proliferation, differentiation, tumorigenesis, and metastasis. The precise regulatory mechanisms of FOXA2 in ESCC progression remain unclear.
MATERIALS AND METHODS
Western blotting, reverse transcription-quantitative polymerase chain reaction, and immunohistochemistry were used to detect the expression level of FOXA2, CCK-8, transwell, and wound healing assays in vitro and xenograft tumor model in vivo were applied to assess the function of FOXA2. RNA-Seq analysis and the following functional assays were used to elucidate the relationship between FOXA2 and proteasome activity.
RESULTS
The expression level of FOXA2 was downregulated in ECSS tissues and cells. Overexpression of FOXA2 in ESCC cells inhibited epithelial-mesenchymal transition in ESCC cells with the upregulation of E-cadherin and downregulation of Vimentin. Meanwhile, overexpression of FOXA2 inhibited the proliferation, migration, and invasion of ESCC cells. Mechanically, proteasome was involved in the ESCC cells proliferation and invasion inhibition induced by FOXA2, and reduced proteasome activity inhibited ESCC cells proliferation and invasion. RNA-Seq analysis identified PSMB9 as a key downstream target, indicating that FOXA2 attenuates proteasome activity by suppressing PSMB9 expression.
CONCLUSION
FOXA2 suppresses ESCC proliferation and invasion by modulating proteasome activity through PSMB9, highlighting its critical role in ESCC progression and its potential as a therapeutic target.
Wenqiang Xia, Ning Li, Chunxia Gong et al.· Cancer Cell International· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
