Insights into next developments in advanced gastric cancer.
The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations.



A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing.



Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.
aClinic of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute and Faculty of Medicine, Masaryk University, Brno, Czech Republic bUniversity Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany.
Radka
R
Obermannová
Florian
F
Lordick
D006801:Humans; D016032:Randomized Controlled Trials as Topic; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*