Renal cell carcinoma (RCC) is a major neoplasm with high incidence in western countries. Tumors are heterogeneous and are composed of differentiated cancer cells, stromal cells, and cancer stem cells (CSCs). CSCs possess two main properties: self-renewal and proliferation. Additionally, they can generate new tumors once transplanted into immunodeficient mice. Several approaches have been described to identify them, through the expression of cell markers, functional assays, or a combination of both. As CSCs are involved in the resistance mechanisms to radio- and chemotherapies, several new strategies have been proposed to directly target CSCs in RCC. One approach drives CSCs to differentiate into cancer cells sensitive to conventional treatments, while the other proposes to eradicate them selectively. A series of innovative therapies aiming at eliminating CSCs have been designed to treat other types of cancer and have not been experimented with on RCC yet, but they reveal themselves to be promising. In conclusion, CSCs are an important player in carcinogenesis and represent a valid target for therapy in RCC patients.
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