Rhein and its derivatives: potential anti-tumor drugs and corresponding targeted mechanism

Cancer remains a major global health threat with high morbidity and mortality, and clinical treatment is plagued by drug resistance, poor efficacy and severe side effects, driving the search for novel anti-tumor agents from natural products. Rhein, a natural anthraquinone abundant in Rheum palmatum and other medicinal plants, has emerged as a promising anti-tumor phytochemical due to its diverse pharmacological activities and multi-target action characteristics. This review systematically summarizes the natural distribution, chemical structure and structural modification strategies of rhein, and further elaborate the core targeted signaling pathways of rhein in exerting anti-tumor effects. Finally, we propose future research directions for rhein and its derivatives, including accelerating preclinical-to-clinical translation, optimizing structural modification and developing targeted delivery systems to reduce side effects and improve therapeutic efficacy.