Progress and current status of molecule-targeted therapy and drug
resistance in gastric cancer

Chen, Zihao; Li, Yong; Tan, Bi-Bo; Zhao, Qingchuan; Fan, Lixia; Li, Fanzhu; Zhao, Xia

doi:10.1358/dot.2020.56.7.3112071

Cited by 51 publications

(37 citation statements)

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“…Claudins are a family of at minimum 27 proteins with roles in maintaining the intercellular tight junction adhesion, which create a paracellular barrier. The impossibility of these molecules to accomplish their function is linked with tumor development and progression (2,3). Different claudins expression may have prognostic value in colon cancer [claudin (CLDN)-1] (4), pancreatic cancer , and hepatocellular carcinoma and thyroid cancer (CLDN-10) (5,6).…”

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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“…In the past few decades, several pivotal regulators are reported to participate in GC's pathogenesis (8,9). For example, METTL3-mediated m 6 A methylation of SPHK2 targets KLF2, thus promoting advanced GC (10). Human CCR4 and CAF1 deacetylase mediate the regulation of human GC cell proliferation and tumorigenicity via modulating the cell cycle process (11).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical stage II or stage III patients require multidisciplinary adjunctive approaches ( 4 , 5 ). The primary contributor to the failure of GC treatment is drug resistance ( 6 , 7 ). In the past few decades, several pivotal regulators are reported to participate in GC’s pathogenesis ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer

Xue

Bei

et al. 2021

Front. Immunol.

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Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.

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“…Gastric cancer is characterized by aggressiveness and a propensity for local recurrence 1 . Currently, oxaliplatin-based chemotherapy, such as XELOX, is the mainstay treatment for controlling local recurrence of gastric cancer after surgery 2 , 3 .…”

Section: Introductionmentioning

confidence: 99%

LINC00963/miR-4458 regulates the effect of oxaliplatin in gastric cancer by mediating autophagic flux through targeting of ATG16L1

Hou

Dong

2021

Sci Rep

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Oxaliplatin resistance is the greatest obstacle to the management of local recurrence in gastric cancer patients after surgery. Accumulating evidence has suggested that inhibiting autophagy may be a novel approach for reversing resistance to oxaliplatin treatment. In this manuscript, we aimed to investigate the role of LINC00963 in regulating autophagy and oxaliplatin resistance. qRT-PCR, immunochemistry staining, and western blotting were used to detect gene expression. Plasmids were used to up- and downregulate the expression of LINC00963 and miR-4458. A caspase 3/7 activity kit and flow cytometry were used to detect the apoptosis rate. CCK8 and Transwell assays were used to test cell proliferation and migration, respectively. Transmission electron microscopy and a dual fluorescent lentivirus autophagy system were used to evaluate autophagic flux. Dual luciferase reporter gene assays and RNA pulldown assays were used to evaluate the potential crosstalk. LINC00963 was highly expressed in gastric cancer patients and cell lines. In addition, high LINC00963 expression was found to be associated with poor prognosis and local recurrence in gastric cancer patients, indicating that LINC00963 might be involved in oxaliplatin resistance. Moreover, we found that LINC00963 was aberrantly highly expressed in oxaliplatin-resistant SGC-7901 (SGC-7901-R) cells and promoted proliferation and migration and reduced the apoptosis rate in SGC-7901-R cells. Furthermore, among all potential target microRNAs, miR-4458 was found to be negatively regulated by LINC00963 both in vivo and in vitro. In addition, miR-4458 overexpression led to impaired proliferation and migration and enhanced cell apoptosis and G1 arrest in SGC-7901-R cells. Further RNA pulldown and dual luciferase reporter gene assays indicated the interaction between LINC00963 and miR-4458. Moreover, we found enhanced autophagic flux in SGC-7901-R cells compared with SGC-7901 cells; in addition, an inhibitor of autophagy induced apoptosis in SGC-7901-R cells. Then, we found that downregulation of LINC00963 expression and upregulation of miR-4458 expression significantly suppressed autophagic flux in SGC-7901-R cells. Based on starBase V3.0 and dual luciferase reporter gene assays, we predicted and confirmed that ATG16L1 might be the target of miR-4458 to regulate autophagy. In conclusion, LINC00963 and miR-4458 are potential biomarkers for predicting the overall survival of gastric cancer patients. Moreover, targeting LINC00963 to inhibit autophagic flux sensitizes gastric cancer cells to oxaliplatin treatment, suggesting that it is a potential novel therapeutic target for improving oxaliplatin sensitivity.

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Progress and current status of molecule-targeted therapy and drug resistance in gastric cancer

Cited by 51 publications

References 0 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

Identification and Validation of the Immune Regulator CXCR4 as a Novel Promising Target for Gastric Cancer

LINC00963/miR-4458 regulates the effect of oxaliplatin in gastric cancer by mediating autophagic flux through targeting of ATG16L1

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