Renal cell carcinoma (RCC) is the most prevalent form of kidney malignancy, with an increasing incidence, and clear-cell RCC representing the majority of cases. Current treatment options, such as immunotherapy, have improved survival rates but are limited by postoperative complications, drug resistance, and adverse effects. Plant-derived natural compounds have gained attention as potential agents for RCC treatment, thanks to their varied biological effects and minimal toxicity. This review systematically examines how these compounds exert anticancer effects through two complementary mechanisms. Ferroptosis and pyroptosis, as novel regulated programmed cell death modalities identified in recent years, provide new therapeutic targets for RCC through their direct cytotoxic effects. The indirect regulation of the tumor microenvironment (TME) and the renin-angiotensin system (RAS) also plays a critical role in cancer progression and therapeutic resistance. The synergistic effects of the aforementioned direct mechanisms and indirect regulation indicate that plant-derived natural compounds can not only eliminate cancer cells but also enhance the sensitivity of tumors to existing therapies. In conclusion, plant-derived natural compounds show significant promise as effective, low-toxicity alternatives or adjuncts in RCC therapy. Their integration into clinical practice could address key challenges like drug resistance and tumor heterogeneity, paving the way for innovative and patient-centered cancer treatments.
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