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

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...

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Bibliographic Details
Published in:Pflügers Archiv 2017-01, Vol.469 (1), p.45-53
Main Authors: Hashimoto, Yosuke, Yagi, Kiyohito, Kondoh, Masuo
Format: Article
Language:English
Subjects:
Animals
Biomedical and Life Sciences
Biomedicine
Cell Biology
Claudins - metabolism
Clostridium perfringens
Enterotoxins - pharmacology
Enterotoxins - therapeutic use
Epithelium - drug effects
Epithelium - metabolism
Human Physiology
Humans
Invited Review
Molecular Medicine
Neoplasms - drug therapy
Neoplasms - metabolism
Neurosciences
Receptors
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Summary: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.
ISSN:0031-6768
1432-2013
DOI:10.1007/s00424-016-1878-6