Carcinoma of the gastroesophageal junction (GEJ) may represent a specific histo-pathological and biologic entity. Most clinical trial data available have emerged by including GEJ cancer either in gastric or esophageal cancer studies. Although surgery and chemotherapy are considered the standard treatment for the disease, numerous questions remain unanswered and there is still much debate. In this article, we discuss the challenges in how to approach an optimal multi-disciplinary treatment including surgery, timing (preoperative, postoperative, peri-operative) and chemotherapeutic regimen, radiotherapy and targeted therapy. More recent advances in genetics, genomics, and next-generation sequencing (NGS) technologies for whole and exome cancer genome sequencing and systems biology approaches are also discussed.
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