Therapeutic targets associated to E-cadherin dysfunction in gastric cancer

Abstract

Introduction: Epithelial cadherin (E-cadherin) plays a key role in epithelial cell-cell adhesion, contributing to tissue differentiation and homeostasis. Throughout the past decades, research has shed light on the molecular mechanisms underlying E-cadherin's role in tumor progression, namely in invasion and metastization. Emerging evidence established E-cadherin as a tumor suppressor and suggests that targeting E-cadherin or downstream signaling molecules may constitute effective cancer therapeutics.

Areas covered: This review aims to cover E-cadherin-mediated signaling during cancer development and progression and highlight putative therapeutic targets.

Expert opinion: Reconstitution of E-cadherin expression or targeting of E-cadherin downstream molecules holds promise in cancer therapies. Considering the high frequency of CDH1 promoter hypermethylation as a second hit in malignant lesions from hereditary diffuse gastric cancer patients, histone deacetylase inhibitors are potential therapeutic agents in combination with conventional chemotherapy, specifically in initial tumor stages. Concerning E-cadherin-mediated signaling, we propose that HER receptors (as epidermal growth factor receptor) and Notch downstream targets are clinically relevant and should be considered in gastric cancer therapeutics and control.