Claudins and Gastric Cancer: An Overview
Abstract
:Simple Summary
Abstract
1. Introduction
2. General Information of CLDNs
3. CLDN Expression in GC
3.1. CLDN18
Type of CLDN | Main Functions, Signaling Molecules Involved, and Clinical Significances in GC | References |
---|---|---|
CLDN1 | - correlation with tumor infiltration and metastasis - Akt, Src, and NF-κB signaling pathway - poor prognostic factor | [39,40] [41,42] [40,43] |
CLDN2 | - CDX2-dependent targeting relationship with CagA produced from H. pylori | [44] |
CLDN3 | - correlation with lymph node metastasis - important immunosuppressive regulator | [45] [46] |
CLDN4 | - correlation with lymph node metastasis - promoting EMT and infiltration of MMP-2 and MMP-9 | [47] [48,49,50] |
CLDN6 | - cell proliferation and migration/infiltration with YAP1 - high expression was positively correlated with decreased OS | [51] [51,52] |
CLDN7 | - proliferation in a CagA-and β-catenin-dependent manner - poor prognostic factor | [53] [54] |
CLDN10 | - association with metastasis and proliferation | [55,56] |
CLDN11 | - correlation with H. pylori infection and Borrmann classification, not with lymph node metastasis and TNM stage | [57] |
CLDN14 | - correlation with lymph node metastasis | [58] |
CLDN17 | - correlation with lymph node metastasis | [58] |
CLDN18 | - correlation with metastasis (lymph node, peritoneal, bone, and liver metastasis) - poor prognostic factor - Wnt, β-catenin, CD44, EFNB/ EPHB receptor signals, and HIPPO signals - CLDN18-ARHGAP fusion in genomically stable type - therapeutic target of Claudiximab (IMAB362, Zolbetuximab) | [59,60] [61,62,63,64,65,66,67,68] [54,69,70] [8] [10,71,72,73] |
CLDN23 | - poor prognostic factor | [57] |
3.2. CLDN1
3.3. CLDN2
3.4. CLDN3
3.5. CLDN4
3.6. CLDN6
3.7. CLDN7
3.8. CLDN10
3.9. CLDN11
3.10. CLDN14
3.11. CLDN17
3.12. CLDN23
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Study Name | NCT Number | Phase | Number of Participants | Design | Response Rate | OS | PFS | Adverse Effects |
---|---|---|---|---|---|---|---|---|
- | NCT00909025 | I | 15 | Single-dose escalation study evaluating safety and tolerability | - | - | - | Vomiting |
PILOT | NCT01671774 | I | 32 | Multiple dose study of IMAB362 with immunomodulation (Zoledronic acid and IL-2) | 11 patients had disease control | 40 weeks | 12.7 weeks | Nausea and vomiting |
MONO | NCT01197885 | IIa | 54 | Multiple dose study of IMAB362 as monotherapy | Clinical benefit rate: 23% | - | - | Nausea, vomiting, and fatigue |
FAST | NCT01630083 | IIb | 246 | Randomized EOX vs. IMAB362 + EOX, extended with high-dose IMAB362 + EOX | Objective response rate: 25 vs. 39% | 8.3 vs. 13.0 months | 5.3 vs. 7.5 months | Neutropenia, anemia, weight loss, and vomiting |
GLOW | NCT03653507 | III | 500 (estimated) | Double-blinded, Randomized, IMAB362 plus CAPOX compared with placebo plus CAPOX as first-line treatment of subjects with CLDN 18.2-positive, HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma | - | - | - | - |
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Hashimoto, I.; Oshima, T. Claudins and Gastric Cancer: An Overview. Cancers 2022, 14, 290. https://doi.org/10.3390/cancers14020290
Hashimoto I, Oshima T. Claudins and Gastric Cancer: An Overview. Cancers. 2022; 14(2):290. https://doi.org/10.3390/cancers14020290
Chicago/Turabian StyleHashimoto, Itaru, and Takashi Oshima. 2022. "Claudins and Gastric Cancer: An Overview" Cancers 14, no. 2: 290. https://doi.org/10.3390/cancers14020290