Journal
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
Volume 469, Issue 1, Pages 45-53Publisher
SPRINGER
DOI: 10.1007/s00424-016-1878-6
Keywords
Clostridium perfringens enterotoxin; Claudin; Tumor therapy; Tumor diagnosis
Categories
Funding
- Ministry of Health, Labour, and Welfare of Japan
- Japan Agency for Medical Research and Development (AMED)
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [24390042]
- Adaptable and Seamless Technology Transfer Program through Target-driven RD Agency
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- Takeda Science Foundation
- Japan Society for the Promotion of Science
- Grants-in-Aid for Scientific Research [15J10065, 24390042] Funding Source: KAKEN
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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.
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