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.