The influence of cell-cell fusion on cancer heterogeneity and its promise for targeted treatments

Cell-cell fusion is a common cellular process that occurs in nature. In the physiological environment, cell-cell fusion plays a crucial role in the establishment of homeostasis and the normal development of an organism. Normal cell-cell fusion is related to zygote formation, placental development, muscle growth, and macrophage formation. However, in cancer, cell-cell fusion destabilizes homeostasis and enhances cancer heterogeneity. The fusion of cancer and normal host cells, such as mesenchymal stem cells or white blood cells, promotes cancer growth, metastasis, and immune escape. On the other hand, fusion of cancer cells with each other leads directly to the formation of polyploid giant cancer cells (PGCCs). PGCCs are cancer stem cells considered the root cause of cancer metastasis, chemoradiotherapy resistance and recurrence. The presence of PGCCs significantly promotes the evolution of cancer. Clinical detection and targeted therapies based on cell-cell fusion have rapidly emerged with advancements in cell culture technology, which may bring hope to the treatment of cancer patients.