The challenge of targeted therapies for gastric cancer patients: the beginning of a long journey.

INTRODUCTION: Despite significant improvements in systemic chemotherapy over the last two decades, the prognosis of patients with advanced disease remains dismal. Collaborative, high-quality research and advances in high-throughput technologies have contributed to elucidate molecular pathways underpinning disease progression and have stimulated many clinical studies testing target therapies in the advanced disease setting. Although progress has been made thanks to trastuzumab in HER2 positive tumours, antiangiogenic drugs have produced conflicting results and EGFR-inhibitors have failed to show major improvements. AREAS COVERED: While commenting on the results of many key Phase III randomized trials, the Authors discuss the most promising classes of novel targeted agents and present the current challenges toward a customized treatment. EXPERT OPINION: Palliative chemotherapy became the worldwide standard of care for patients with advanced gastric cancers, producing significant life prolongation and improvement of life quality. Nevertheless, long-term outcomes of those patients remain poor. Because of the encouraging advancement in novel targeted therapies, such a disappointing scenario is now evolving. While results serve as a springboard for future research, more comprehensive efforts are needed to clarify the biological mechanisms underpinning cancer progression and help clinicians to develop new effective treatments.