The potential for targeting HER2 therapeutically in esophageal cancer - a grasp at straws?

INTRODUCTION: Human EGFR-2 (HER2) has an impact on cellular proliferation and survival. HER2 overexpression has been shown to be a marker for poorer prognosis in several malignancies. Trastuzumab, a humanized mAb, is successfully used to target HER2 in breast cancer. The effect of targeting HER2 in esophageal cancer (EC) is the focus of current trials.

AREAS COVERED: Basic knowledge, detection techniques and definitions of HER2 overexpression, as well as the molecular mechanisms underlying the effects of trastuzumab on HER2, are reviewed. An overview of research on the prognostic and predictive relevance of HER2 in EC is given, as well as an overview of current trials targeting HER2 in EC.

EXPERT OPINION: The first aim of novel targeted therapies must be perioperative neoadjuvant and adjuvant applications, as surgery is the only option for curative treatment in patients with stage I - III EC. Regarding targeted therapies in EC, HER2 is currently the most promising target. Trials of trimodal neoadjuvant therapy regimes (neoadjuvant radiochemotherapy plus trastuzumab) are currently recruiting. However, the prognostic impact of HER2 overexpression in EC remains ambiguous. Targeting HER2 may have negative and positive impacts on survival, depending on which subgroup of EC patients is treated.