Natural compounds regulating MAPK-related signaling pathways: potential intervention strategies for gastric cancer

Gastric cancer (GC) is a common malignant tumor of the digestive system, and its progression involves multiple molecular factors and signaling pathways. Dysregulation of mitogen-activated protein kinase (MAPK)-related signaling pathways is closely associated with the proliferation, invasion, metastasis, and drug resistance of GC. This review summarizes the major upstream factors associated with MAPK dysregulation, including Helicobacter pylori infection, genetic mutations, Epstein-Barr virus (EBV) infection, and epigenetic regulation. In addition, this review explores MAPK-related biological processes, including autophagy, oxidative stress, apoptosis, epithelial-mesenchymal transition (EMT), and cell cycle arrest. This paper focuses specifically on natural compounds capable of modulating ERK, JNK, and p38 MAPK-related signaling, as well as their interactions with other signaling networks, including PI3K/Akt, JAK/STAT3, and reactive oxygen species (ROS). Current evidence is primarily derived from preclinical studies; direct validation of target binding is limited, and significant gaps remain regarding pharmacokinetics, bioavailability, safety, and clinical translation. Therefore, further mechanistic and translational studies are needed to elucidate the therapeutic potential of natural compounds that modulate MAPK-related signaling pathways in GC.