Gastric cancer remains one of the most frequent and lethal cancers worldwide, as a consequence of aging and lack of screening programs. Moreover, the detailed mechanisms underlying gastric carcinogenesis have yet to be disclosed, which impairs accurate predictions of patient outcome and effective therapeutic strategies. In the last year, we have witnessed the emergence of new data that reinforce the complex interplay between microbes and other risk factors in the development of this disease. In particular, basic and clinical investigations have elucidated oncogenic mechanisms exerted by Helicobacter pylori and Epstein-Barr virus infection, involving the activation of pro-inflammatory signaling and acquisition of genomic instability. The gastric microbial community was also found to modify the stomach microenvironment, yielding distinct morphological and biochemical profiles that promote gastric carcinogenesis.

Herein, we selected relevant studies published from April 2021 to March 2022, and provided an overview of novel pathways and molecular programs underlying gastric cancer development and therapy resistance. Ultimately, we shall discuss how this knowledge may improve classification systems, and highlight potential molecules as therapeutic targets or as prognostic biomarkers.