Esophageal carcinoma: are modern targeted therapies shaking the rock?

Abstract

Purpose of review: Our current review aims to outline recent progress in the development of modern targeted therapeutic regimens for esophageal cancer.

Recent findings: Esophageal cancers demonstrate marked molecular heterogeneity. Modern technology increasingly allows us to identify subgroups of patients whose tumors fit particular molecular profiles. Tumor-based human epidermal growth factor receptor 2 (HER-2) analysis has become a standard part of the work-up for patients with tumors of the esophagogastric junction. The anti-HER-2 antibody, trastuzumab, when added to a chemotherapeutic regimen combining a fluoropyrimidine and platinum, provides a survival benefit for those patients with HER-2 overexpression and/or amplification. Despite large coordinated efforts to establish the efficacy of additional targeted therapeutics, to this point minimal additional benefit has been realized in affecting prominent molecular targets, such as vascular endothelial growth factor and epidermal growth factor receptor, in esophageal cancer. Multiple targets of interest remain under investigation with some early encouraging data. These targets include mammalian target of rapamycin, c-MET, insulin like growth factor 1 receptor and cytotoxic T-lymphocyte antigen 4. Additional improvements in therapy may stem from improved patient selection for combinations of standard cytotoxic regimens, such as platinum-based regimens.

Summary: Targeted therapeutics have yielded early benefit, but further progress will require a deeper understanding of this disease, improved identification of subpopulations who may derive greater benefit, and continued multicenter efforts to conduct the necessary clinical investigations.