Treatment options for patients with esophageal cancer are limited and the overall survival is disappointing. While surgical resection remains the only curative treatment option, there is a need for innovative medical therapies to extend patient survival. The tumor microenvironment represents an interesting target for the development of new treatment strategies. The tumor microenvironment consists of different cell types including immune, inflammatory, and stromal cells. In the past two decades many potential targets for the treatment of esophageal cancers were evaluated in preclinical experiments and transferred into clinical trials.In this chapter of the book, we will provide an overview of in vitro data, preclinical animal studies, and translational research on the role of the tumor microenvironment in the development and treatment of esophageal cancer. In particular, we will discuss the impact of inflammatory cytokines like interleukins. Preclinical mouse models with interleukin overexpression develop Barrett lesions in the esophagus and clinical studies have shown an association between an interleukin overexpression in human tumors and shortened overall survival.Beside the inflammatory cells in the tumor microenvironment, recent preclinical studies have shown an important role for stem cells in the development of esophageal carcinoma. In this chapter we summarize the current research on stem cells in the development of esophageal cancer and highlight potential therapeutic options. In addition, we will discuss the role of angiogenesis and anti-angiogenic therapy in the development and treatment of esophageal cancer. In the last section of this chapter, we provide an overview of current clinical trials that investigate the therapeutic potential of the tumor microenvironment.
Keywords: Angiogenesis; Barrett esophagus; Cancer cell lines; Clinical trials; Esophageal cancer; Fibroblasts; Interleukin-1; Interleukin-6; Macrophages; Mouse models; Pericytes; Preclinical models; Stem cells; Translational research; Tumor microenvironment.