&lt;p&gt;Pathological Complete Response After a Single Dose of Anti-PD-1 Therapy in Combination with Chemotherapy as a First-Line Setting in an Unresectable Locally Advanced Gastric Cancer with PD-L1 Positive and Microsatellite Instability&lt;/p&gt;

Jin, Hailong; Li, Peijie; Mao, Chenyu; Zhu, Kan; Chen, Hai; Gao, Yuan; Yu, Jiren

doi:10.2147/ott.s243298

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…A potential mechanism underlying this difference is the elevated expression of PD-L1 in the cancer patients with the mutation of these genes. To date, many studies have revealed that PD-L1 expression is a predictive biomarker for anti-PD-1/PD-L1 immunotherapy in GC patients (53,54). A clinical trial study (KEYNOTE-059) revealed that pembrolizumab, an anti-PD-1 monoclonal antibody, had encouraging antitumor activity in PD-L1-positive advanced gastric/gastroesophageal cancer patients (53).…”

Section: Discussionmentioning

confidence: 99%

“…A clinical trial study (KEYNOTE-059) revealed that pembrolizumab, an anti-PD-1 monoclonal antibody, had encouraging antitumor activity in PD-L1-positive advanced gastric/gastroesophageal cancer patients (53). Jin et al reported that a PD-L1-positive unresectable locally advanced GC with MSI exhibited pathological complete response to a single dose of anti-PD-1 immunotherapy in combination with chemotherapy (54). Hence, the identification of gene mutations associated with tumor immunity may furnish biomarkers for the optimal stratification of GC patients responsive to immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

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Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Yin¹,

Wang²

2020

Ann Transl Med

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Background: Although immunotherapy has achieved success in treating various refractory malignancies including gastric cancers (GCs) with DNA mismatch repair deficiency, only a subset of cancer patients are responsive to immunotherapy. Therefore, the identification of useful biomarkers or interventional targets for improving cancer immunotherapy response is urgently needed. Methods:We investigated the associations between various molecular features and immune signatures using three multi-omics GC datasets. These molecular features included genes, microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins, and pathways, and the immune signatures included CD8+ T cell infiltration, immune cytolytic activity (ICA), and PD-L1 expression. Moreover, we investigated the association between gene mutations and survival prognosis in a gastrointestinal (GI) cancer cohort receiving immunotherapy and two GC cohorts not receiving such a therapy. Results:The mutations of some important oncogenes and tumor suppressor genes were appreciably associated with immune signatures in GC, including PIK3CA, MTOR, RNF213, TP53, ARID1A, PTEN, ATM, and CDH1. Moreover, a number of genes exhibited a significant expression correlation with immune signatures in GC, including CXCL9,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Yin¹,

Wang²

2020

Ann Transl Med

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“…However, few clinical trials have been carried out on the application of ICI as neoadjuvant treatment in GC, and only one clinical trial (NCT03064490) is registered in ClinicalTrials.gov. Jin et al [ 61 ] submitted a notable case report, in which a patient with PD-L1 positive and MSI-high advanced GC (cT4aN+M0 state) received a single dose of anti-PD-1 therapy in combination with chemotherapy and radical gastrectomy, resulting in a pathological complete response (pT0N0M0)[ 61 ]. This case report suggested that a combined ICI scheme might be feasible as neoadjuvant treatment of GC.…”

Section: Prospects Of Icis For Neoadjuvant Treatment Of Gcmentioning

confidence: 99%

Research status on immunotherapy trials of gastric cancer

Liang¹,

Wu²,

Yu³

et al. 2021

WJCC

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The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.

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“…Therefore, it is urgent to explore new treatment methods. Blockers targeting PD‐L1, 3 PD‐1, 4 HER2, 5 and other targets have become an important direction in study of GC. Overexpression of HER2 in GC patients is often positively correlated with PD‐L1 expression, which could depend on the PI3K‐AKT‐mTOR pathway, 6 suggesting that the combination of drugs aimed at the above targets might be a new therapeutic pathway.…”

Section: Introductionmentioning

confidence: 99%

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer

Jin

et al. 2021

Cancer Science

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Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with Kd values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.

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<p>Pathological Complete Response After a Single Dose of Anti-PD-1 Therapy in Combination with Chemotherapy as a First-Line Setting in an Unresectable Locally Advanced Gastric Cancer with PD-L1 Positive and Microsatellite Instability</p>

Cited by 10 publications

References 19 publications

Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Identification of molecular features correlating with tumor immunity in gastric cancer by multi-omics data analysis

Research status on immunotherapy trials of gastric cancer

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer

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