Re‐evaluating Stem Cell Roles in Homeostasis and Cancer of the Esophagus

The localization and identity of esophageal stem cells remain highly debated, prompting the emergence of several hypotheses. Although early models proposed a homogeneous basal progenitor layer, recent evidence suggests a heterogeneous pool of stem/progenitor cells with diverse phenotypic and functional characteristics. We present a perspective on this heterogeneity and its implications for both normal tissue maintenance and disease susceptibility. Esophageal cancers can emerge as a result of random mutations or the activity of cancer stem cells (CSCs). The multifaceted interactions between genetic predisposition and environmental influences demonstrate that cancer onset can be driven not only by cell phenotype but also by various external pressures. Advances in in vivo and in vitro models now offer valuable tools to explore these stem cell dynamics and may pave the way for novel therapeutic approaches in esophageal cancer treatment.