The role of Chinese medicines in targeting non-coding RNAs to overcome cancer drug resistance: Mechanisms and clinical translation challenges

As a major obstacle in cancer treatment, drug resistance is increasingly recognized that non-coding RNA (ncRNA) plays an important role in regulating cell plasticity. This review comprehensively explores how ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs, drive drug resistance by altering identity plasticity (epithelial-mesenchymal transition and stemness), state plasticity (cell fate selection and metabolic reprogramming), and communication plasticity in the tumor microenvironment. Due to the complexity of the ncRNA network, Chinese medicines (CMs) with multi-target properties have become a potential modulator. Preclinical evidence suggests that certain CMs and their bioactive compounds have been shown to inhibit therapeutic resistance by regulating various ncRNAs. For instance, curcumin upregulates miR-206 to inhibit the JAK/STAT3 pathway in colorectal cancer, while in gastric cancer, β-elemene inhibits miR-1323 to prevent EGFR-driven epithelial-mesenchymal transition. However, current clinical research is still in the preliminary exploration stage and lacks high-quality, large-scale, prospective randomized controlled trials. CONCLUSIONS: From a mechanistic perspective, CMs targeting ncRNAs present a potential multi-target strategy against cancer drug resistance, but their clinical translation remains largely theoretical. Bridging this gap requires future research to prioritize in-depth mechanism studies, advanced delivery systems, and rigorous clinical validation related to ncRNA biomarkers. CHEMICAL COMPOUNDS IN THIS ARTICLE: Curcumin; Berberine; β-Elemene; Astragaloside IV; Icariin; Matrine; Toosendanin; Artesunate; Resveratrol; Cantharidin.