Abstract 5457: High levels of fatty acid synthase expression in esophageal cancers represent a potential target for therapy

Abstract

Abstract Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. To investigate the expression of this candidate target in esophageal cancer, we evaluated expression of FAS protein in - cases of esophageal squamous cancer, - cases of esophageal adenocarcinoma, and - cases of Barrett's esophagus with dysplasia - a lesion thought to represent a pre-invasive precursor to esophageal cancer. Using immunohistochemistry, we found significantly higher levels of FAS expression in -% of the squamous cancers and -% of the adenocarcinomas compared to normal esophageal epithelium. To evaluate the potential for inhibiting this enzyme as a treatment of esophageal cancer, we treated mice bearing xenografts of the Colo680N (squamous carcinoma) and Bic1 (adenocarcinoma) cell lines using C93, a rationally designed molecule that inhibits FAS activity. In these experiments, C93 significantly inhibited the growth of orthotopic xenograft tumors from without causing anorexia and weight loss in the treated animals. We conclude that, similar to several other common types of human cancer, FAS is expressed at very high levels in esophageal cancer, and growth of these cancers can be inhibited by pharmacological agents that target this enzyme. Moreover, this high expression of FAS is also seen in pre-invasive lesions of the esophagus, leading us to propose considering of FAS-inhibitors for purposes of esophageal cancer chemoprevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5457.