Target therapies and notably monoclonal antibodies are currently being considered for esophageal, gastric, and
gastroesophageal junction cancers. EGFR was found to be overexpressed in 60-86% of gastric or gastroesophageal tumors
and in 50-70% of esophageal cancers. Cetuximab was shown to be a radiosensitizing agent in the treatment of ENT neoplasia.
These results led to several phase II encouraging therapeutic trials evaluating the combination of cetuximab with
radiochemotherapy in locally advanced esophageal cancers. Numerous encouraging phase II trials evaluating cetuximab
combined with chemotherapy in patients with gastric adenocarcinoma or gastroesophageal junction cancer were reported.
These promising results are still to be confirmed by the ongoing phase III trials. Several studies reported HER2 overexpression
in gastric cancer (7-34%), which appeared to be associated with poorer prognosis. Trastuzumab is a monoclonal
antibody directed against the extracellular HER2 domain. The international phase III trial known as ToGA (Trastuzumab
for Gastric Cancer) aimed to determine the clinical efficacy and acceptable toxicity profile of trastuzumab in combination
with first-line chemotherapy in HER2-overexpressing gastric or gastroesophageal cancer. Angiogenesis is an essential
step in the initial phase of tumorigenesis, and it is normally absent from healthy tissues except for particular physiological
situations, such as wound healing. VEGF-A plays a role in endothelial growth and angiogenesis. Bevacizumab, a humanized
monoclonal anti-VEGF-A antibody, is currently being studied for gastric cancer. The phase III AVAGAST study,
evaluating bevacizumab in association with chemotherapy in advanced gastric adenocarcinoma, did not achieve its primary
aim of improved OS in bevacizumab-treated patients.