title: Roles of the first-generation claudin binder, Clostridium perfringens enterotoxin, in the diagnosis and claudin-targeted treatment of epithelium-derived cancers.
abstract: Given that most malignant tumors are derived from epithelium, developing a strategy for treatment of epithelium-derived cancers (i.e., carcinomas) is a pivotal issue in cancer therapy. Carcinomas, including ovarian, breast, prostate, and pancreatic cancers, are known to overexpress various claudins (CLDNs); in particular, CLDN-3 and -4 are frequently overexpressed in malignant case. The generation of CLDN binders is a key for expanding CLDN-targeted cancer therapy but has been delayed due to the small size of CLDN extracellular domains (approximately 50 amino acids for the first domain and 15 amino acids for the second) and their high homology among species. Interestingly, however, the receptors for Clostridium perfringens enterotoxin (CPE), a foodborne toxin in humans, happen to be identical to CLDN-3 and -4. Thus, the first CLDN binder, CPE, has provided us CLDN-targeted cancer therapy from a concept into a potential reality. In this review, we describe roles of CPE technology in cancer therapy and discuss future directions in the CLDN-targeting concept-to-therapy process.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan. masuo@phs.osaka-u.ac.jp.
authors.forename: Masuo
authors.identifier: 0000-0001-5624-1135
authors.initials: M
authors.lastname: Kondoh
mesh_terms: D000818:Animals; D057167:Claudins / Q000378:metabolism*; D004768:Enterotoxins / Q000494:pharmacology* / Q000627:therapeutic use*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D057167:Claudins; D004768:Enterotoxins; C035598:enterotoxin, Clostridium
keywords: Claudin; Clostridium perfringens enterotoxin; Tumor diagnosis; Tumor therapy