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Esophageal cancer (EC) is a worldwide healthcare concern and represents an aggressive malignancy. Squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) are the two primary histological subtypes but have yet to vastly differ in management. Outcomes remain poor with current treatment approaches; however, recent progress is focused on distinguishing separate targets based on thistology. Here we provide an overview of EC management via a historical review and recent discoveries. As noted in this review, targeted therapy has lagged behind other solid tumors. Over the previous decade, for EACs there were only two targeted therapies used in the advanced setting with limited benefits. ESCC progress was rather non-existent. We present current ongoing advancements that have occurred in the realm of immunotherapy and emerging new agents. It is becoming clearer that segregating these two histological subtypes in trials should be the goal of future trial designs. ESCC appears to be more amenable to immune modulation than EAC; however, we are navigating in exciting times as molecular interrogations of EC has expanded with the hope of making more rapid progress. There is still hard work ahead of us to painfully define subsets representing heterogeneity and then finding appropriate agents.

Esophageal cancer: emerging therapeutics