&lt;p&gt;The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer&lt;/p&gt;

Zhang, Wanjun; Niu, Junwei; Ma, Yongcheng; Yang, Xinrong; Cao, Huixia; Guo, Honggang; Bao, Fengchang; Ahmed, Hafiz Abdul Waqas; Chen, Yuqing; Sun, Kai

doi:10.2147/ott.s240721

Cited by 12 publications

(6 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The antitumor formulation of CHI, as an HDACi, was mainly administrated orally or intraperitoneally, which usually needed a high dosage such as 25 mg/kg. 49 In this study, we achieved a decreased dosage for CHI through a liposome delivery system via systematic administration, which was expected to attenuate the potential toxicity. To investigate the dose-dependent antitumor efficiency, 4T1 tumor-bearing mice were i.v.…”

Section: 7mentioning

confidence: 99%

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade

Wang

et al. 2021

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Improving tumor immunogenicity is critical for increasing the responsiveness of triple-negative breast cancer (TNBC) to anti-PD-(L)1 treatment. Here, we verified that chidamide (CHI), an epigenetic modulator, could elicit immunogenic cell death within TNBC to enhance cancer immunogenicity and elicit an antitumor immune response. Additionally, CHI increased the expression level of PD-L1, MHC I, and MHC II on cancer cells, which contributed to T-cell recognition and PD-1/ PD-L1 blockade therapy response. The synergistic antitumor efficacy of CHI and PD-L1 blockade therapy was further explored through liposomes co-delivering CHI and BMS-202 (a smallmolecule PD-L1 inhibitor). The liposomes possessed good biocompatibility, security, and controllable drug release and endowed therapeutics drugs with favorable tumor accumulation. Furthermore, the drug-loaded liposomes could obviously boost the antitumor immunity of TNBC through CHI-enhanced tumor immunogenicity and BMS-202-mediated PD-L1 blockade, thereby effectively inhibiting the growth of primary and metastatic tumors with an inhibitory rate of metastasis of up to 96%. In summary, this work provided a referable and optional approach for clinical antitumor therapy based on the combination of an epigenetic modulator and PD-1/PD-L1 blockade therapy.

show abstract

Section: 7mentioning

confidence: 99%

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade

Wang

et al. 2021

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…The chemotherapy drugs are generally used in combination to enhance the treatment effect and reduce the drug resistance of patients. For example, chidamide combined with bortezomib has the effect of anti-cancer GC ( Zhang et al, 2020 ). However, the specific mechanism and efficacy of these drugs in GC still require further explored.…”

Section: Discussionmentioning

confidence: 99%

HIPPO signaling-related signature for predicting prognosis and therapeutic response in gastric cancer

et al. 2023

View full text Add to dashboard Cite

Background: Gastric cancer (GC) is a multifactorial progressive disease with high mortality and heterogeneous prognosis. Effective prognostic biomarkers for GC were critically needed. Hippo signaling pathway is one of the critical mechanisms regulating the occurrence and development of GC, and has potential clinical application value for the prognosis and treatment of GC patients. However, there is no effective signature based on Hippo signaling pathway-related genes (HSPRGs) to predict the prognosis and treatment response of GC patients. Our study aimed to build a HSPRGs signature and explore its performance in improving prognostic assessment and drug therapeutic response in GC.Methods: Based on gene expression profiles obtained from The Cancer Genome Atlas (TCGA) database, we identified differentially expressed HSPRGs and conducted univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct a multigene risk signature. Subsequently, the Kaplan-Meier curve and receiver operating characteristic (ROC) were performed to evaluate the predictive value of the risk signature in both training and validation cohort. Furthermore, we carried out univariate and multivariate Cox regression analysis to investigate the independent prognostic factors and establish a predictive nomogram. The enriched signaling pathways in risk signature were analyzed by gene set enrichment analysis (GSEA). Tumor immune dysfunction and exclusion (TIDE) and drug sensitivity analysis were performed to depict therapeutic response in GC.Results: In total, 38 differentially expressed HSPRGs were identified, and final four genes (DLG3, TGFB3, TGFBR1, FZD6) were incorporated to build the signature. The ROC curve with average 1-, 3-, and 5-year areas under the curve (AUC) equal to .609, .634, and .639. Clinical ROC curve revealed that risk signature was superior to other clinicopathological factors in predicting prognosis. Calibration curves and C-index (.655) of nomogram showed excellent consistency. Besides, in the immunotherapy analysis, exclusion (p < 2.22 × 10–16) and microsatellite instability (p = .0058) performed significantly differences. Finally, our results suggested that patients in the high-risk group were more sensitive to specific chemotherapeutic agents.Conclusion: Results support the hypothesis that Hippo-related signature is a novel prognostic biomarker and predictor, which could help optimize GC prognostic stratification and inform clinical medication decisions.

show abstract

“…Moreover, low-risk cases were more sensitive to AZ628, Bortezomib, CHIR.99021, Cyclopamine, and GW843682X, with higher sensitivity to AZD8055, Bosutinib, RO.3306, Sunitinib, and VX.702. Among these therapeutic compounds, Bortezomib in synergy with other chemotherapeutic agents can improve the therapeutic effects against gastric cancer (Bae et al, 2008;Zhang et al, 2020). Cyclopamine sensitizes TRAIL-resistant gastric cancer cells to TRAIL-induced apoptosis through endoplasmic reticulum stress-induced upregulation of death receptor 5 and survivin degradation (Na et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer

Kong

Wang

2023

Front. Genet.

View full text Add to dashboard Cite

Objective: The current molecular classification system for gastric cancer covers genomic, molecular, and morphological characteristics. Non-etheless, classification of gastric cancer based upon DNA damage repair is still lacking. Here, we defined DNA damage repair-based subtypes across gastric cancer and identified clinicopathological, tumor microenvironment and pharmacogenomic features.Methods: Unsupervised clustering analysis was executed in the TCGA-STAD cohort based upon the transcriptional expression profiling of DNA damage repair genes. LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature. The identified subtypes or signature were externally verified in the GSE84426 or GSE84433 cohort. The transcriptional levels of immunomodulators, abundance of immune cells and somatic mutations were measured, respectively. Immunotherapeutic response, and drug sensitivity were investigated. The DNA damage repair-relevant genes were further experimentally verified.Results: Two DNA damage repair-based subtypes were identified, with the notable heterogeneity in prognostic stratification, tumor microenvironment and somatic mutations. The gene signature was generated for risk stratification and prognostic prediction, which was in relation to immunomodulators and immune cells. High-risk cases were more likely to respond to immunotherapy, with distinct pharmacogenomic landscapes between low- and high-risk groups. Higher levels of PAPPA2, MPO, MAGEA11, DEPP1, CPZ, and COLEC12 and lower level of CYTL1 were proven in gastric cancer cells versus controls. Silencing CYTL1 facilitated intracellular ROS accumulation and suppressed migration in gastric cancer cells.Conclusion: Collectively, the DNA damage repair-based classification is a suitable complement to existing molecular classification system, and the quantitative gene signature provides a robust tool in selecting specific therapeutic options.

show abstract

<p>The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer</p>

Cited by 12 publications

References 37 publications

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade

Combination of Chidamide-Mediated Epigenetic Modulation with Immunotherapy: Boosting Tumor Immunogenicity and Response to PD-1/PD-L1 Blockade

HIPPO signaling-related signature for predicting prognosis and therapeutic response in gastric cancer

Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer

Contact Info

Product

Resources

About