Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View

SIMPLE SUMMARY: During the last several years, gastric cancer has been extensively studied on the molecular level and distinct molecular subtypes have been defined accordingly. Here, we review the current data on targeted treatment approaches for advanced or metastatic gastric cancer based on molecular alterations or immunological features, ranging from clinically approved treatment strategies to more innovative concepts which are currently in preclinical or clinical development. Information on the translational context and methodology is also provided, holding promise for the further improved development of personalized treatment strategies in the future. ABSTRACT: Gastric cancer is a leading cause of cancer death worldwide. Systemic treatment comprising chemotherapy and targeted therapy is the standard of care in advanced/metastatic gastric cancer. Comprehensive molecular characterization of gastric adenocarcinomas by the TCGA Consortium and ACRG has resulted in the definition of distinct molecular subtypes. These efforts have in parallel built a basis for the development of novel molecularly stratified treatment approaches. Based on this molecular characterization, an increasing number of specific genomic alterations can potentially serve as treatment targets. Consequently, the development of promising compounds is ongoing. In this review, key molecular alterations in gastric and gastroesophageal junction cancers will be addressed. Finally, the current status of the translation of targeted therapy towards clinical applications will be reviewed.