An emerging targeted strategy for gastric cancer: the multi-pathway regulatory potential of Chinese medicine monomers

Gastric cancer (GC) ranks as the fifth most common malignancy worldwide, characterized by high incidence and poor prognosis. While current therapeutic approaches continue to evolve, their efficacy remains limited by issues such as drug resistance, adverse effects, and recurrence. Substantial evidence indicates that the pathogenesis and progression of GC are closely associated with the dysregulation of multiple key signaling pathways, including Hedgehog, Notch, PI3K/AKT, and Wnt/β-catenin. As active compounds derived from natural products, Chinese medicine monomers (CMMs) have emerged as a highly promising complementary treatment strategy due to their multi-targeting capabilities and favorable safety profiles. However, existing reviews have largely focused on single pathways or compounds, lacking a systematic analysis of multi-target synergistic regulation and the bottlenecks in clinical translation. This review systematically collates the literature published over the past 5 years (2021-2025) in CNKI, PubMed, and Web of Science. Moving beyond the previous research paradigm centered on single pathways or compounds, our aim was to systematically elucidate the molecular mechanisms by which CMMs exert their anti-GC effects through the synergistic regulation of multiple key signaling pathways. Integrated analysis demonstrates that various CMMs can effectively inhibit tumor cell proliferation, migration, and invasion by targeting these critical pathways. Their principal antitumor mechanisms involve the induction of various forms of programmed cell death-including apoptosis, autophagy, pyroptosis, and ferroptosis-while also enhancing sensitivity to conventional chemotherapy. Importantly, novel nanodelivery systems show strong potential to significantly improve the bioavailability and tumor-targeting efficiency of these monomers. In summary, CMMs offer a unique multi-targeted approach to GC treatment through synergistic pathway regulation. Future research should focus on the precise identification of molecular targets, the advancement of clinical translation, the conduct of rigorous clinical trials, and an in-depth exploration of the synergistic effects of nanotechnology-based CMMs.