Roles of the first-generation claudin binder, Clostridium perfringens enterotoxin, in the diagnosis and claudin-targeted treatment of epithelium-derived cancers

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• 作者：Yosuke Hashimoto ; Kiyohito Yagi…
• 关键词：Clostridium perfringens enterotoxin ; Claudin ; Tumor therapy ; Tumor diagnosis
• 刊名：Pflügers Archiv - European Journal of Physiology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：469
• 期：1
• 页码：45-53
• 全文大小：
• 刊物主题：Human Physiology; Molecular Medicine; Neurosciences; Cell Biology; Receptors;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013
• 卷排序：469

文摘

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.