| Target Gene Symbol | Disease Subtype (ESCC/EAC/Both) | Association Score | Key Role/Function | Therapeutic Relevance | Clinical Stage |
|---|---|---:|---|---|---|
| PDCD1 (PD-1) | Both; especially ESCC | 0.608 (carcinoma of esophagus); 0.607 (ESCC) | Immune checkpoint receptor on T cells; central mediator of T-cell exhaustion in the tumor microenvironment | Established biomarker/target for anti-PD-1 immunotherapy; anti-PD-1 plus platinum-based chemotherapy is standard first-line in advanced disease; adjuvant nivolumab improves DFS after neoadjuvant CRT and surgery | Approved (OpenTargets approval evidence; nivolumab/pembrolizumab clinical use) (pqac-00000000, pqac-00000020, pqac-00000018) |
| TP53 | Both | 0.539 (carcinoma of esophagus); 0.422 (ESCC) | Master tumor suppressor controlling DNA-damage response, apoptosis, and genomic stability; most frequently altered driver in EC | Primarily prognostic/biologic rather than directly actionable; informs pathogenesis, progression, and resistance biology | Biomarker / investigational target (pqac-00000000, pqac-00000022, pqac-00000025) |
| ADH1B | Mainly ESCC / susceptibility across carcinoma of esophagus | 0.530 (carcinoma of esophagus) | Alcohol metabolism enzyme; inherited variation modifies acetaldehyde exposure and alcohol-related carcinogenic risk | Risk stratification and prevention relevance rather than direct tumor targeting | Genetic susceptibility marker (pqac-00000000, pqac-00000003) |
| NFE2L2 (NRF2) | Predominantly ESCC | 0.522 (carcinoma of esophagus) | Oxidative-stress transcriptional program; pathway activation supports survival, detoxification, and therapy resistance | Candidate target for resistant ESCC biology; pathway status may guide future precision strategies | Preclinical / investigational (pqac-00000000, pqac-00000021, pqac-00000022) |
| EGFR | Both; more emphasized in ESCC and subset of EAC | 0.512 (carcinoma of esophagus); 0.454 (ESCC) | Receptor tyrosine kinase driving proliferation, survival, and invasion | Overexpressed in a subset; cetuximab and EGFR-directed approaches studied, but clinical benefit has been inconsistent | Investigational / limited clinical utility (pqac-00000000, pqac-00000019) |
| FGFR1 | Predominantly ESCC / carcinoma of esophagus | 0.511 (carcinoma of esophagus) | RTK signaling contributor; copy-number gain/amplification in subsets | Potential actionable amplification in selected tumors; not standard of care | Investigational (pqac-00000000) |
| ERBB2 (HER2) | Predominantly EAC | 0.503 (carcinoma of esophagus); 0.457 (EAC) | RTK amplified in a molecular subset of EAC; promotes oncogenic signaling and chromosomal-instability phenotype | Established predictive biomarker; trastuzumab-based therapy for HER2-positive disease; companion diagnostics required | Approved in HER2-positive adenocarcinoma (pqac-00000000, pqac-00000010, pqac-00000025) |
| MTOR | Both / carcinoma of esophagus | 0.499 (carcinoma of esophagus) | Central kinase in PI3K-AKT-mTOR signaling controlling growth, metabolism, and survival | Pathway is biologically important, but mTOR inhibitors are not standard therapy in EC | Investigational (pqac-00000000, pqac-00000022) |
| CDKN2A | Both; especially Barrett's/EAC evolution and ESCC cell-cycle dysregulation | 0.696 (esophageal disorder) | Tumor suppressor controlling G1/S checkpoint; inactivation/loss is an early event in progression | Strong biomarker of progression biology; informs early carcinogenesis and possible prevention/risk models | Biomarker / investigational (pqac-00000000, pqac-00000022, pqac-00000024) |
| PIK3CA | Both | 0.658 (esophageal disorder) | Catalytic PI3K subunit; activates PI3K-AKT signaling, promoting proliferation, survival, invasion, and metastasis | Actionable in principle; pathway inhibitors are relevant in basket/precision-oncology settings, but not routine EC standard | Investigational / precision-oncology candidate (pqac-00000000, pqac-00000022) |
| NOTCH1 | Predominantly ESCC, but also implicated in EAC evolution | Not numerically listed in OpenTargets top rows here | Context-dependent driver in squamous epithelium; mutation/activation affects lineage fitness, angiogenesis, and tumor progression | Valuable biologic stratifier; no standard NOTCH-directed EC therapy | Investigational (pqac-00000022, pqac-00000023, pqac-00000021) |
| SMAD4 | Predominantly EAC | 0.645 (esophageal disorder) | TGF-β pathway tumor suppressor; recurrently altered in EAC and linked to progression from Barrett's neoplasia | Biomarker of aggressive biology and progression; not yet a standard direct therapeutic target | Biomarker / investigational (pqac-00000000, pqac-00000023, pqac-00000026) |
| CD274 (PD-L1) | Predominantly ESCC but relevant to both | 0.478 (ESCC) | Ligand for PD-1; key immune-evasion marker within inflamed tumors and myeloid-rich microenvironments | FDA-approved companion/selection biomarker for checkpoint blockade in some settings; expression associated with immunotherapy stratification | Approved companion biomarker / therapeutic axis (pqac-00000000, pqac-00000010, pqac-00000040) |
| ARID1A | Mainly EAC / esophageal disorder | 0.622 (esophageal disorder) | Chromatin-remodeling tumor suppressor; contributes to epigenetic dysregulation and genomic instability | Emerging biomarker for molecular subclassification and synthetic-lethality concepts; not standard EC target | Investigational (pqac-00000000, pqac-00000025) |


*Table: This table summarizes major disease-target associations for esophageal carcinoma by integrating OpenTargets association scores with recent literature on subtype biology and therapeutic relevance. It is useful for prioritizing biomarkers and targets across ESCC and EAC, including established immunotherapy and HER2-directed axes as well as investigational pathways.*