Cancer Stem Cells in Esophageal Squamous Cell Carcinoma: A Path to Understanding

The sixth most common cancer in developing countries is the esophageal squamous cell carcinoma (ESCC), with a poor prognosis because the 5-year survival rate of patients with ESCC is only 35%. The incidence of ESCC is influenced by various factors, including diet, genetics, environmental exposures, and socio-economic status; almost all biological drivers of ESCC involve cancer stem cells (CSCs), which drive tumor initiation, therapy resistance, recurrence, and metastasis. CSC-related biomarkers in ESCC provide useful information on prognosis, diagnosis, and treatment methods. The accessory characteristics that identify CSCs are unique enzymatic activity, surface markers, and drug resistance; hence, contributing to their ability to overcome traditional forms of chemotherapy and radiotherapy. These biomarkers not only enable the isolation of CSCs but are also highly correlated with the clinical outcome of ESCC. A multiconjugation of certain CSC markers can improve detection accuracy and inform more precise treatment strategies. In addition, the development of ESCC-specific CSC biomarkers has the potential to develop targeted immunotherapy, which will eventually result in better patient outcomes. A CSC-based therapeutic approach provides a holistic understanding of CSC biology and the development of comprehensive treatment options for ESCC. Although several studies have investigated CSCs across various contexts, a comprehensive review focusing on their role, biomarkers, and therapeutic potential in ESCC is currently lacking, and this review aims to address that gap.