Targeted therapy and novel agents for the treatment of gastric cancer: A view toward the future

Multimodal treatment of resectable gastric cancer has been standardized including R0–D2 gastrectomy and adjuvant treatment. For advanced gastric cancer, several molecular agents have been evaluated in well–conducted randomized studies. The most important is represented by trastuzumab, a monoclonal antibody, which has shown significant antitumor activity against human epidermal growth factor receptor (Her)–2–positive advanced gastric cancer. Recently it has been established that the HER2 positive subgroup disease benefits from targeted therapy with trastuzumab. However, a substantial fraction of these patients who account for 25 % of all patients develop recurrence while for the remaining 75 % no targeted therapy exists. Therefore, there is now the crucial need for the development of more effective drugs and for the identification of predictive and prognostic biomarkers to select in an appropriate way those patients who will benefit from specific therapies. Nowadays, an alternative is offered by the single agent trastuzumab–emtansine (T–DM1). T–DMI provides increased therapeutic efficacy in HER2 positive breast cancer setting and we hope that similar results are achieved in HER2 positive gastric cancer. Clinical next generation sequencing (NGS) analyses provides the opportunity for understanding therapeutic resistance mechanism and developing next generation biomarkers and drugs.