Esophageal Adenocarcinoma Methods and Protocols

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Alfred K. Lam (ed.), Esophageal Adenocarcinoma: Methods and Protocols, Methods in Molecular Biology, vol. 1756,
https://doi.org/10.1007/978-1-4939-7734-5_5, © Springer Science+Business Media, LLC 2018

Chapter 5

Target Therapy for Esophageal Adenocarcinoma

Ka-On Lam and Dora L. W. Kwong

Abstract

Adenocarcinoma of the esophagus is a deadly disease and median survival of patients with metastatic dis-
ease is around 1 year only. There is an unmet need to personalize treatment by identifying molecular tar-
gets and respective target therapy in esophageal adenocarcinoma. There has been success in targeting the
human epidermal growth factor receptor 2 (HER2) and vasoendothelial growth factor (VEGF) pathway
while more failures were encountered in the clinical studies targeting epidermal growth factor (EGFR),
mammalian target of rapamycin (mTOR), and mesenchymal-epithelial transition (MET). Studies using
immune-checkpoint inhibitors have shown early success, and we await mature data for clinical application.
In the chapter, the target therapy and novel treatment strategy will be reviewed. In the future, it is hoped
that advances in translational research in targeted therapy against esophageal adenocarcinoma will bring
about new progress in clinical practice.

Key words Esophageal, Esophagogastric, Adenocarcinoma, Palliative, Target therapy, Immunotherapy

1 Introduction

Metastatic esophageal and esophagogastric junction adenocarcinomas

are universally fatal. Treatment with chemotherapy improves qual-

ity of life and prolongs survival [ 1 ]. However, patients in reported

landmark chemotherapy studies only survive a median of

9–13 months [ 2 – 4 ]. Personalized medicine is the priority for

improving treatment outcomes but identification of predictive and

prognostic biomarkers has so far been disappointing. Matthews

and colleagues suggested that COX-2, CD3, CD8, and EGFR to be

potential makers with largest survival effects in a meta- analysis [ 5 ].

However, there is a lack of high-quality robust clinical studies. A

genome to protein approach would be better suited for the devel-

opment and subsequent validation for biomarkers. In a recent

paper published by The Cancer Genome Atlas Research Network,

comprehensive molecular analysis of 164 esophageal carcinomas,

359 gastric adenocarcinomas, and 36 additional adenocarcino-

mas of the esophagogastric junction was performed to define

molecular subgroups and deciphers potential therapeutic targets [ 6 ].