Lei Li

Dormant tumor cells, major contributors to tumor recurrence and metastasis, are characterized by cell cycle arrest and reactivation potential. Tumor dormancy arises from the dynamic interplay between intrinsic tumor properties and extrinsic factors within the tumor ecosystem. This ecosystem operates at two distinct levels: the tumor microenvironment (TME) and the systemic macroenvironment (SME). Within the dormant TME, tumor cells engage in complex interactions with surrounding stromal cells, extracellular matrix components, and the vasculature, which are mediated through growth factors, cytokines, and metabolic byproducts. At the systemic level, the SME modulates tumor dormancy via inflammatory responses, metabolic homeostasis, hormonal regulation, and neural signaling. The TME and SME collectively maintain tumor dormancy through their bidirectional crosstalk. Disruption of this delicate ecological equilibrium can trigger tumor reactivation and metastatic progression. Consequently, effective therapeutic strategies should simultaneously target both TME remodeling and SME modulation. In this review, we provide a comprehensive analysis of the coordinated roles of the TME and SME in regulating tumor cell dormancy and reactivation while summarizing potential therapeutic approaches and clinical trials aimed at either eliminating dormant tumor cells or sustaining dormancy. Consequently, we propose a novel two-dimensional combined treatment strategy that concurrently addresses both the TME and SME to prevent tumor recurrence and metastasis.

LTBP2 neutralization enhances paclitaxel sensitivity in vitro and in vivo

Cox proportional hazard regression analyses for overall survival

Cox proportional hazard regression analyses for progressive free survival

CAF-derived LTBP2 promotes proliferation and migration in CAFs and enhances migration and chemoresistance in ESCC cells

Integrated analysis of LTBP2 expression

Flow cytometry analysis of bone marrow cells in mice under combination treatments

LTBP2 promotes migration and chemoresistance in ESCC cells independent of TGF-β1 signaling

Anti–integrin α6 or anti–integrin β4 antibody treatment mitigates ESCC cell migration and enhances chemotherapy sensitivity

Association of LTBP2 expression with clinicopathological features in ESCC