The pathogenesis of gastric cancer is complex and related to multiple factors. Dysregulation of intracellular signaling pathways represents a common pathogenic mechanism and may be amenable to drug targeting. Multiple well-established oncogenic pathways, such as those mediated by cell cycle regulators, nuclear factor-kappaB, cyclooxygenase-2 and epidermal growth factor receptor are implicated in gastric carcinogenesis. Emerging evidence also underscores the importance of signaling pathways involved in the developmental process, including transforming growth factor-beta/bone morphogenetic protein signaling, Wnt/beta-catenin signaling, Hedgehog signaling and Notch signaling. Understanding their biological significance will provide a rational basis for drug development. Their relative importance and cross-talk in gastric carcinogenesis, however, are still not completely understood and warrant further investigation.
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