Targeting tumor dormancy: the next frontier in gastrointestinal stromal tumor therapy.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the digestive tract, are primarily driven by mutations in KIT/PDGFRA. The remarkable success of tyrosine kinase inhibitors such as imatinib (IM) in treating GIST has established them as a paradigm of precision medicine in modern oncology. However, acquired resistance to IM remains a major cause of poor prognosis in GIST patients. Exploring novel mechanisms of IM resistance is critically important for improving outcomes. Tumor dormancy and cancer stem cell (CSC) models, observed across multiple malignancies, are closely linked to therapy resistance, tumor recurrence, and metastasis. Emerging evidence suggests that analogous non-genetic persistence states also exist in GIST, including dormant cells and KITlow stem-like/CSC-like subpopulations. This review summarizes the fundamental regulatory mechanisms of tumor dormancy and CSC biology, discusses their candidate manifestations in GIST, and proposes innovative therapeutic strategies based on these insights.