Esophageal cancer: from pathogenesis to precision therapies
Summary
Esophageal cancer (EC), encompassing primarily esophageal squamous-cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), continues to pose a significant global health burden, which is largely due to delayed diagnosis and limited therapeutic efficacy. In this review, we synthesize current insights into key aspects of EC, including established risk factors, the stepwise process of tumorigenesis, strategies for early detection and prevention, and emerging therapeutic approaches. Emphasis
Content
# Esophageal cancer: from pathogenesis to precision therapies
*Published: 2026 Apr 15*
Esophageal cancer (EC), encompassing primarily esophageal squamous-cell
carcinoma (ESCC) and esophageal adenocarcinoma (EAC), continues to pose a
significant global health burden, which is largely due to delayed diagnosis and
limited therapeutic efficacy. In this review, we synthesize current insights
into key aspects of EC, including established risk factors, the stepwise process
of tumorigenesis, strategies for early detection and prevention, and emerging
therapeutic approaches. Emphasis is particularly placed on the molecular
underpinnings of (1) early tumor initiation and malignant progression, with a
focus on genetic mutations, epigenetic modifications, and alterations within the
tumor microenvironment; (2) the clonal expansion and metabolic reprogramming
that play essential roles in shaping the evolutionary trajectory of esophageal
cancer, thereby promoting intratumoral heterogeneity; (3) the transition from
normal epithelium to invasive carcinoma in both ESCC and EAC driven by
sequential disruptions of molecular networks governing epithelial homeostasis;
and (4) advances in early screening techniques and minimally invasive
interventions that may offer new opportunities for EC prevention and early
detection, especially in high-risk populations. In addition, we summarize recent
progress in precision treatment, including chemotherapy, targeted therapy,
immunotherapy, and multidisciplinary treatment. By delineating the molecular and
cellular mechanisms underlying EC initiation and progression, this review aims
to inform future directions in early diagnosis, risk stratification, and
individualized therapy, ultimately contributing to improved clinical outcomes
and precision prevention of EC.
DOI: 10.1038/s41392-026-02614-7