Fusion of tumor cells and mesenchymal stem/stroma cells: a source of tumor heterogeneity, evolution and recurrence

The heterogeneity and evolution of tumors remain significant obstacles in cancer treatment, contributing to both therapy resistance and relapse. Mesenchymal stem/stromal cells (MSCs) are multipotent stromal cells within the tumor microenvironment that interact with tumor cells through various mechanisms, including cell fusion. While previous research has largely focused on the effects of MSC-tumor cell fusion on tumor proliferation, migration, and tumorigenicity, emerging evidence indicates that its role in tumor maintenance, evolution, and recurrence, particularly under stress conditions, may be even more pivotal. This review examines the connection between MSC-tumor cell fusion and several critical factors like tumor heterogeneity, cancer stem cells, and therapy resistance, highlighting the crucial role of cell fusion in tumor survival, evolution, and recurrence. Additionally, we explore potential therapeutic strategies aimed at targeting this process.