Editorial: Unraveling GI cancer heterogeneity through single-cell multi-omics approaches

Gastrointestinal (GI) cancers represent a significant global health burden, accounting for 26% of cancer incidence and 35% of all cancer-related deaths (Arnold et al., 2020). While the primary sites—colorectum, stomach, liver, esophagus, and pancreas—are functionally diverse, they share a common epithelial origin and are linked within the same physiological system. The challenge in treating these malignancies lies in their profound genetic and phenotypic heterogeneity, as well as the complex interplay between malignant cells and their surrounding tumor microenvironment (TME) (Zhang et al., 2022). In addition there has been a recent worldwide surge in incidence in younger individuals, with still unknown etiology (Xia et al., 2025). This Research Topic highlights the transformative power of single-cell technologies and spatial transcriptomics in decoding these complexities. By capturing a variety of genomic data, the collected research offers an integrated view of the mechanisms driving tumor initiation, progression, and therapeutic response. It is important to note the typical limitations of these types of studies which include small sample sizes and a need to validate published results.