Targeted therapies have been studied in combination with chemoradiation therapy for esophageal and gastroesophageal junction cancers. To date, the Human Epidermal Growth Factor Receptor 2 (HER2) HER2, epidermal growth factor receptor, and vascular endothelial growth factor pathways have been most extensively studied in esophagogastric cancers. However, despite strong preclinical rationale and evidence of activity in other diseases, the efficacy of these agents has been mixed when studied in the metastatic setting or in combination with chemoradiation. In this review, the history of the development of targeted therapies in esophagogastric cancers is reviewed, with a specific focus on the incorporation of these agents with chemoradiation. Additionally, more recently identified targets of interest in esophagogastric cancers, including c-MET, heat shock protein 90, and Sonic hedgehog, are discussed in the context of chemoradiation.
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