Molecular Mechanisms and Therapeutic Targets of Traditional Chinese Medicine Compounds in Renal Cell Carcinoma: A Comprehensive Narrative Review

ETHNOPHARMACOLOGICAL RELEVANCE: Advanced renal cell carcinoma (RCC) often stops responding to targeted drugs, and those drugs can be toxic. Traditional Chinese Medicine (TCM) works differently: it hits many targets at once and tries to rebalance the whole body. That makes TCM a plausible add-on, not a replacement. AIM OF THE REVIEW: This review aims to comprehensively summarize and critically appraise the molecular mechanisms by which TCM components and formulas exert anti-RCC activities, focusing on key signaling pathways, non-apoptotic cell death, reversal of drug resistance, and potential synergy with conventional treatments. METHODS: We searched PubMed, Web of Science, Embase, Scopus, and CNKI, covering studies published from January 2015 to January 2026. Search terms included "renal cell carcinoma" (MeSH/title/abstract), "traditional Chinese medicine", "natural product", "phytochemical", and "signaling pathway", applied in Boolean combination. Studies were included if they reported molecular-level mechanistic data for TCM-derived compounds or formulas in RCC cell lines, animal models, or clinical settings; studies reporting only descriptive ethnobotanical data without mechanistic investigation, conference abstracts without full data, or non-peer-reviewed sources were excluded. Due to the heterogeneity of study designs across the included literature, this work is framed as a comprehensive narrative review rather than a formal systematic review, and findings should be interpreted accordingly. RESULTS: TCM-derived compounds inhibit RCC proliferation by modulating the PI3K/AKT/mTOR, MAPK/ERK, and NF-κB pathways. They also induce ferroptosis and necroptosis, reverse sunitinib resistance, and enhance anti-PD-L1 immunotherapy. TCM formulas target hub genes such as CCND1, PTGS2, and ABCG2. However, most studies lack pharmacokinetic data and rigorous clinical validation. CONCLUSION: TCM acts as a multi-target network modulator against RCC. That could help overcome drug resistance and improve current therapies. Future research should focus on chemical standardization, pharmacokinetic profiling, and biomarker-driven clinical trials.