Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer

Zhang, Jianwei; Dong, Ruilan; Shen, Lin

doi:10.21147/j.issn.1000-9604.2020.02.13

Cited by 35 publications

(32 citation statements)

References 16 publications

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“…After IMAB362 binds to CLDN 18.2, immune effectors activate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. This change induces apoptosis and promotes the inhibition of cell proliferation, with beneficial effects for patients ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

et al. 2021

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An increasing number of tumor markers have been discovered to have potential efficacy as diagnostic and prognostic tools in gastric cancer. We aimed to assess putative correlations between claudin 18.2 expression and pathological or prognosis features in patients with gastric cancer. MEDLINE, Web of Science, EBSCO, and ClinicalTrials.gov were used to search for relevant studies from their inception to 30 October 2020. Finally, a total of six articles were included in this meta-analysis. Review Manager 5 software was applied to examine the heterogeneity among the studies and to calculate the odds ratio with 95% CI by selecting corresponding models, in evaluating the strength of the relationship. Publication bias test was also conducted. No bias and no significant correlations were found between CLDN 18.2 and TNM stages, Lauren classification, HER2, grading, or overall survival. This meta-analysis expounded that the relationship with CLDN 18.2 and pathological features depends on the percentage of staining of tumor cells for which CLDN 18.2 is considered positive. Our pooled outcomes suggest that targeted therapy for CLDN 18.2 could be effective if certain criteria were established.

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Section: Introductionmentioning

confidence: 99%

Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

et al. 2021

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“…CLDN18 protein is involved in the formation of tight junctions in epithelial cells [18]. A CLDN18 protein subtype, CLDN18.2, is the specific CLDN18 expressed in the stomach and is an important component of the gastric acid barrier [19][20][21][22]. Zolbetuximab, formerly ideal monoclonal antibody 362 (IMAB362), is a new type of immunoglobulin G1 antibody that is highly specific for the CLDN18.2 protein [22][23][24].…”

Section: Arhgap26 In Gastric Cancermentioning

confidence: 99%

“…A CLDN18 protein subtype, CLDN18.2, is the specific CLDN18 expressed in the stomach and is an important component of the gastric acid barrier [19][20][21][22]. Zolbetuximab, formerly ideal monoclonal antibody 362 (IMAB362), is a new type of immunoglobulin G1 antibody that is highly specific for the CLDN18.2 protein [22][23][24]. Thus, it has the potential to be used in targeted therapy for gastric cancer patients with the CLDN18-ARHGAP26 fusion gene.…”

Section: Arhgap26 In Gastric Cancermentioning

confidence: 99%

“…The schematic shows how GEFs, GAPs, and GDIs regulate the cycle of the Rho GTPase signaling pathway and the associated cell behaviors. GEF guanine nucleotide exchange factor, GAP GTPase-activating protein; GDI Rho GDP dissociation inhibitor and plays a crucial role in the gastric acid barrier [19][20][21][22]. The CLDN18-ARHGAP26 fusion protein only has the transmembrane domain of CLDN18 and lacks the cytoplasmic part at the C-terminus.…”

Section: Mechanism Of Arhgap26 In Cancersmentioning

confidence: 99%

“…The answer to this question will determine whether this fusion gene can be used as a specific indicator of tumors that would be sensitive to Zolbetuximab-targeted therapy [17]. In addition, given the differences between the Eastern and Western populations, Zolbetuximab in combination with other chemotherapies exerts a greater toxicity in Asian people than in other populations [22]. Therefore, the tolerability and therapeutic effect of the combination of Zolbetuximab and other chemotherapeutics in the Asian population still needs to be evaluated.…”

Section: Issues To Be Solvedmentioning

confidence: 99%

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The role of GTPase-activating protein ARHGAP26 in human cancers

et al. 2021

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Rho GTPases are molecular switches that play an important role in regulating the behavior of a variety of tumor cells. RhoA GTPase-activating protein 26 (ARHGAP26) is a GTPase-activating protein and inhibits the activity of Rho GTPases by promoting the hydrolytic ability of Rho GTPases. It also affects tumorigenesis and progression of various tumors through several methods, including formation of abnormal fusion genes and circular RNA. This review summarizes the biological functions and molecular mechanisms of ARHGAP26 in different tumors, proposes the potential clinical value of ARHGAP26 in cancer treatment, and discusses current issues that need to be addressed.

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Claudin18.2 expression and clinicopathological features in cytology effusion specimens from gastric adenocarcinoma: A comparative study with tissue specimens

Dai

Zheng

Jin

et al. 2023

Cancer Cytopathology

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Background: Zolbetuximab (IMAB362) is under investigation for treating advanced gastrointestinal tumors because it targets Claudin18.2 (CLDN18.2). CLDN18.2 is a promising molecule along with the presence of human epidermal growth factor receptor 2 in gastric cancer. This study evaluated cell block (CB) preparations of serous cavity effusions for the feasibility for CLDN18.2 protein expression and compared the results with those of biopsy or resection specimens. The association of CLDN18.2 expression in effusion samples and the clinicopathological features were also investigated.Methods: Cytological effusion specimens and matched surgical pathology biopsy or resection specimens of 43 gastric and gastroesophageal junctional cancer cases were stained for CLDN18.2 expression and quantified using immunohistochemistry based on the manufacturer's instructions. Results:Positive staining was detected in 34 (79.1%) tissue and 27 (62.8%) effusion CB samples in this study. When "positivity" was defined as moderate-to-strong staining in ≥40% viable tumor cells, CLDN18.2 expression was observed in 24 (55.8%) tissue and 22 (51.2%) effusion CB samples. A cutoff of 40% for CLDN18.2 positivity was used to demonstrate high concordance (83.7%) between cytology CB and tissue specimens. The results showed that CLDN18.2 expression in effusion specimens correlated with tumor size (p = .021) but not with sex, age at diagnosis, primary tumor location, staging, Lauren phenotype, cytomorphologic features, or Epstein-Barr virus infection. Cytological effusions with or without CLDN18.2 expression did not significantly affect overall survival.Conclusions: This study's results show that serous body cavity effusions may be suitable for CLDN18.2 biomarker testing; however, discordant cases should be interpreted cautiously.

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Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer

Cited by 35 publications

References 16 publications

Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

Clinicopathologic Relevance of Claudin 18.2 Expression in Gastric Cancer: A Meta-Analysis

The role of GTPase-activating protein ARHGAP26 in human cancers

Claudin18.2 expression and clinicopathological features in cytology effusion specimens from gastric adenocarcinoma: A comparative study with tissue specimens

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