N-cadherin as a therapeutic target in cancer.
During tumor progression, cancer cells undergo dramatic changes in the expression profile of adhesion molecules resulting in detachment from original tissue and acquisition of a highly motile and invasive phenotype. A hallmark of this change, also referred to as the epithelial-mesenchymal transition, is the loss of E- (epithelial) cadherin and the de novo expression of N- (neural) cadherin adhesion molecules. N-cadherin promotes tumor cell survival, migration and invasion, and a high level of its expression is often associated with poor prognosis. N-cadherin is also expressed in endothelial cells and plays an essential role in the maturation and stabilization of normal vessels and tumor-associated angiogenic vessels. Increasing experimental evidence suggests that N-cadherin is a potential therapeutic target in cancer. A peptidic N-cadherin antagonist (ADH-1) has been developed and has entered clinical testing. In this review, the authors discuss the biochemical and functional features of N-cadherin, its potential role in cancer and angiogenesis, and summarize the preclinical and clinical results achieved with ADH-1.
Mariotti
Agnese
A
Centre Pluridisciplinaire d'Oncologie, Division of Experimental Oncology, Lausanne Cancer Center, and Swiss Institute for Experimental Cancer Research (ISREC), NCCR Molecular Oncology, Epalinges, Switzerland. agnese.mariotti@isrec.ch
Perotti
Antonella
A
Sessa
Cristiana
C
Rüegg
Curzio
C
D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry
D015820:Cadherins; C495232:HAV peptide; D009842:Oligopeptides