Predictive biomarkers in gastric cancer.

Predictive biomarkers are the mainstay of precision medicine. This review summarizes the advancements in tissue-based diagnostic biomarkers for gastric cancer, which is considered the leading cause of cancer-related deaths worldwide. A disease seen in the elderly, it is often diagnosed at an advanced stage, thereby limiting therapeutic options. In Western countries, neoadjuvant/perioperative (radio-)chemotherapy is administered, and adjuvant chemotherapy is administered in the East. The morpho-molecular classification of gastric cancer has opened novel avenues identifying Epstein-Barr-Virus (EBV)-positive, microsatellite instable, genomically stable and chromosomal instable gastric cancers. In chromosomal instable tumors, receptor tyrosine kinases (RKTs) (e.g., EGFR, FGFR2, HER2, and MET) are frequently overexpressed. Gastric cancers such as microsatellite instable and EBV-positive types often express immune checkpoint molecules, such as PD-L1 and VISTA. Genomically stable tumors show alterations in claudin 18.2. Next-generation sequencing is increasingly being used to search for druggable targets in advanced palliative settings. However, most tissue-based biomarkers of gastric cancer carry the risk of a sampling error due to intratumoral heterogeneity, and adequate tissue sampling is of paramount importance.