Targeting claudins in cancer

Jemal, A. et al. Cancer statistics, 2008. CA Cancer J. Clin. 58, 71–96 (2008).

PubMed  Google Scholar 

Furuse, M., Sasaki, H., Fujimoto, K. & Tsukita, S. A single gene product, claudin-1 or -2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J. Cell Biol. 143, 391–401 (1998). This study demonstrated that expression of a single claudin gene (CLDN-1 or CLDN-2) is sufficient to reconstitute tight junction strand networks and recruit occludin in fibroblasts, establishing claudins as the core structural components of tight junctions.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Furuse, M., Fujita, K., Hiiragi, T., Fujimoto, K. & Tsukita, S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J. Cell Biol. 141, 1539–1550 (1998).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sonoda, N. et al. Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: evidence for direct involvement of claudins in tight junction barrier. J. Cell Biol. 147, 195–204 (1999). This study provided direct evidence that specific claudins are essential components of tight junction barrier function by showing that a Clostridium perfringens enterotoxin C-terminal fragment selectively removes CLND-3 and CLDN-4 from tight junction strands, leading to barrier disruption.

Article  PubMed  PubMed Central  Google Scholar 

Katahira, J., Inoue, N., Horiguchi, Y., Matsuda, M. & Sugimoto, N. Molecular cloning and functional characterization of the receptor for Clostridium perfringens enterotoxin. J. Cell Biol. 136, 1239–1247 (1997). This study was the first to clone and functionally characterize the host cell receptor for Clostridium perfringens enterotoxin, establishing the molecular basis for toxin binding and its role in disrupting tight junctions via claudin family interactions.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gress, T. M. et al. A pancreatic cancer-specific expression profile. Oncogene 13, 1819–1830 (1996).

CAS  PubMed  Google Scholar 

Geng, M. M. et al. Use of representational difference analysis to study the effect of TGFB on the expression profile of a pancreatic cancer cell line. Genes Chromosomes Cancer 26, 70–79 (1999).

Article  CAS  PubMed  Google Scholar 

Michl, P. et al. Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology 121, 678–684 (2001).

Article  CAS  PubMed  Google Scholar 

Kondoh, M., Yoshida, T., Kakutani, H. & Yagi, K. Targeting tight junction proteins — significance for drug development. Drug. Discov. Today 13, 180–186 (2008).

Article  CAS  PubMed  Google Scholar 

Tsukita, S., Tanaka, H. & Tamura, A. The claudins: from tight junctions to biological systems. Trends Biochem. Sci. 44, 141–152 (2019).

Article  CAS  PubMed  Google Scholar 

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. Pflug. Arch. 469, 45–53 (2017).

Article  CAS  Google Scholar 

Shitara, K. et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet 401, 1655–1668 (2023). This phase III trial established CLDN-18.2 as a clinically actionable target by showing survival benefit of zolbetuximab plus chemotherapy in gastric cancer.

Article  CAS  PubMed  Google Scholar 

Klempner, S. J. et al. ILUSTRO: phase II multicohort trial of zolbetuximab in patients with advanced or metastatic claudin 18.2-positive gastric or gastroesophageal junction adenocarcinoma. Clin. Cancer Res. 29, 3882–3891 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McDermott, M. S. J. et al. Preclinical efficacy of the antibody-drug conjugate CLDN6-23-ADC for the treatment of CLDN6-positive solid tumors. Clin. Cancer Res. 29, 2131–2143 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shah, M. A. et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat. Med. 29, 2133–2141 (2023). This phase III trial confirmed CLDN-18.2 as a clinically relevant target by demonstrating survival benefit of zolbetuximab in advanced gastric cancer.

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Laarhoven, H. W. M. & Derks, S. Claudin-18.2 targeting by zolbetuximab: results of SPOTLIGHT in perspective. Lancet 401, 1630–1631 (2023).

Article  PubMed  Google Scholar 

Zhu, G. et al. Targeting CLDN18.2 by CD3 bispecific and ADC modalities for the treatments of gastric and pancreatic cancer. Sci. Rep. 9, 8420 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Jiang, H. et al. Claudin18.2-specific chimeric antigen receptor engineered T cells for the treatment of gastric cancer. J. Natl Cancer Inst. 111, 409–418 (2019).

Article  PubMed  Google Scholar 

Mineta, K. et al. Predicted expansion of the claudin multigene family. FEBS Lett. 585, 606–612 (2011).

Article  CAS  PubMed  Google Scholar 

Morita, K., Furuse, M., Fujimoto, K. & Tsukita, S. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc. Natl Acad. Sci. USA 96, 511–516 (1999).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Suzuki, H. et al. Crystal structure of a claudin provides insight into the architecture of tight junctions. Science 344, 304–307 (2014). This study provided the first high-resolution crystal structure of a mammalian claudin, revealing key architectural features of tight junction proteins and offering structural insight into how claudins form paracellular ion pathways.

Article  CAS  PubMed  Google Scholar 

Itoh, M. et al. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J. Cell Biol. 147, 1351–1363 (1999).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harris, B. Z. & Lim, W. A. Mechanism and role of PDZ domains in signaling complex assembly. J. Cell Sci. 114, 3219–3231 (2001).

Article  CAS  PubMed  Google Scholar 

Tsukita, S., Furuse, M. & Itoh, M. Multifunctional strands in tight junctions. Nat. Rev. Mol. Cell Biol. 2, 285–293 (2001).

Article  CAS  PubMed  Google Scholar 

Suzuki, H., Tani, K. & Fujiyoshi, Y. Crystal structures of claudins: insights into their intermolecular interactions. Ann. NY Acad. Sci. 1397, 25–34 (2017).

Article  CAS  PubMed  Google Scholar 

Morita, K., Sasaki, H., Furuse, M. & Tsukita, S. Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J. Cell Biol. 147, 185–194 (1999).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gow, A. et al. CNS myelin and Sertoli cell tight junction strands are absent in Osp/claudin-11 null mice. Cell 99, 649–659 (1999).

Article  CAS  PubMed  Google Scholar 

Günzel, D. & Yu, A. S. Claudins and the modulation of tight junction permeability. Physiol. Rev. 93, 525–569 (2013).

Article  PubMed  PubMed Central  Google Scholar 

Tamura, A. & Tsukita, S. Paracellular barrier and channel functions of TJ claudins in organizing biological systems: advances in the field of barriology revealed in knockout mice. Semin. Cell Dev. Biol. 36, 177–185 (2014).

Article  CAS  PubMed  Google Scholar 

Nitta, T. et al. Size-selective loosening of the blood–brain barrier in claudin-5-deficient mice. J. Cell Biol. 161, 653–660 (2003).

Article  CAS  PubMed  PubMed Central 

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