[Novel pharmaceutical treatment approaches for gastric cancer]

Abstract

This review article delineates novel approaches for the pharmaceutical treatment of gastric cancer. A newly developed molecular classification of gastric cancer based on histology, genetic, epigenetic and proteomic characteristics has evolved. It provides a road map for development of new drugs and combinations as well as for patient stratification in clinical research and it is expected to be introduced into clinical practice in the near future. Anti-HER2 targeted treatment is a validated strategy for treatment of metastatic gastric cancer and is now also being studied in the perioperative setting to increase response rates and ultimately survival in patients undergoing curative surgery; however, the resistance mechanisms of HER2-targeted treatment are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is a novel concept in the management of advanced gastric cancer. Ramucirumab is an antibody against vascular endothelial growth factor receptor 2 (VEGFR2) and prolongs survival in second-line treatment as a monotherapy and also in combination with paclitaxel; however, biomarkers for selection of patients who particularly benefit from antiangiogenic treatment are still lacking. Immune checkpoint blockade and inhibition of cancer stem cell targets are two emerging principles for the medicinal treatment of gastric cancer. Large-scale international studies for evaluation of these treatment approaches are ongoing. In summary, promising biology-based treatment strategies are evolving; however, tumor heterogeneity, which is an inherent feature of gastric cancer is a particular challenge for the development of targeted medications and a personalized treatment.

Keywords: Anti-HER2; Chemotherapy; Genetics; Immunotherapy; Targeted therapy.