ArticleCancers2025
Synergistic Disruption of Survival and Metastatic Potential in Esophageal Adenocarcinoma Cells Through Combined Inhibition of HIF1α and CD73.
Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- The tumor microenvironment: a dynamic ecosystem and therapeutic nexus in modern oncology.Frontiers in pharmacology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
objectivesHypoxia promotes esophageal adenocarcinoma (EAC) aggressiveness through stabilization of hypoxia-inducible factor-1α (HIF-1α), which regulates pro-survival, pro-metastatic, and immunosuppressive pathways, including the ectoenzyme CD73 (NT5E). Although CD73 is a known hypoxia-responsive gene, its functional integration with HIF-1α signaling in EAC remains incompletely understood. This study aimed to define the relationship between HIF-1α and CD73 in EAC and to evaluate the therapeutic potential of their combined inhibition.
methodsGene expression and survival analyses were performed using CCLE and TCGA-ESCA datasets. CD73 and HIF-1α expression were evaluated in EAC patient tissues by immunohistochemistry. EAC cell lines were subjected to hypoxic conditions with genetic or pharmacologic inhibition of HIF-1α and/or CD73. Cell viability, migration, angiogenesis, VEGF secretion, and purinergic metabolite levels were assessed using luminescence assays, Boyden chamber migration assays, endothelial tube formation assays, ELISA, and targeted LC-MS/MS, respectively.
resultsNT5E expression was transcriptionally upregulated by HIF-1α under hypoxia and correlated with advanced disease stage and poor overall survival in EAC patients. While CD73 inhibition alone modestly reduced EAC cell viability, combined inhibition of HIF-1α and CD73 synergistically decreased tumor cell survival, particularly under hypoxic conditions, and significantly altered extracellular adenosine metabolism. Dual targeting further suppressed migration, reduced VEGF secretion, and impaired angiogenic signaling, indicating disruption of tumor microenvironmental pathways critical for metastasis and immune evasion.
conclusionsThese findings identify CD73 as a direct hypoxia-responsive effector of HIF-1α in EAC and demonstrate that dual inhibition of HIF-1α and CD73 synergistically disrupts tumor cell survival and pro-metastatic signaling. This combinatorial strategy represents a mechanistically integrated therapeutic approach to overcome hypoxia-driven resistance in esophageal adenocarcinoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.