Radiotherapy, EMP and dormancy in TME: An integrated perspective on tumor microenvironments and long-term relapse

Radiotherapy (RT) remains one of the most common modalities for curative treatment, with most cancer patients receiving RT during their treatment periods. Although there have been significant improvements in local targeting, local and distant recurrences after RT still remain a major clinical challenge. Dormant tumor cells, which are characterized by quiescent cells, are a potential driver of local recurrence and metastasis after RT. Epithelial-mesenchymal plasticity (EMP) is a central mechanism that allows disseminated tumor cells (DTCs) to enter a dormant state and reawaken to form recurrences years later. This review summarizes current knowledge of the molecular relationship between RT, EMP, and metastatic dormancy. We discuss the possibility whether RT modulates metastasis and dormancy. Ultimately, we propose promising therapeutic strategies to block RT-mediated metastasis and prevent long-term relapse in distant organs.