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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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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.

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Acknowledgments

We thank all of the members of our laboratory for their useful comments. This work was supported by a Health and Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare of Japan; a research grant from the Japan Agency for Medical Research and Development (AMED); a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan [grant number 24390042]; and funds from the Adaptable and Seamless Technology Transfer Program through Target-driven R&D Agency; Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan; and the Takeda Science Foundation. Y.H. is supported by a Research Fellowship for Young Scientists from the Japan Society for the Promotion of Science.

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  1. Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, 565-0871, Japan

    Yosuke Hashimoto, Kiyohito Yagi & Masuo Kondoh

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  1. Yosuke Hashimoto
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  2. Kiyohito Yagi
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  3. Masuo Kondoh
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Correspondence to Masuo Kondoh.

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Hashimoto, Y., Yagi, K. & Kondoh, M. Roles of the first-generation claudin binder, Clostridium perfringens enterotoxin, in the diagnosis and claudin-targeted treatment of epithelium-derived cancers. Pflugers Arch - Eur J Physiol 469, 45–53 (2017). https://doi.org/10.1007/s00424-016-1878-6

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  • DOI: https://doi.org/10.1007/s00424-016-1878-6

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