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Although several large clinical trials have been conducted in order to investigate targeted inhibition of several molecular pathways in gastric cancer, only a limited number of targeted therapies have been introduced in clinical routine. Besides scientific interest, international guidelines recommend investigation of some distinct molecular alterations, which are associated with therapeutic consequences. These are (i) human epidermal growth factor receptor 2 (HER2), (ii) programmed death receptor 1 (PD-L1) and (iii) microsatellite instability (MSI). There are some emerging markers, such as Epstein–Barr virus (EBV), which might also be associated with a favorable response to immunotherapy. These routine and potential markers will be further discussed in the scope of this short review.