Comprehensive multi‐omics analysis of resectable locally advanced gastric cancer: Assessing response to neoadjuvant camrelizumab and chemotherapy in a single‐center, open‐label, single‐arm phase II trial

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(5)

Published: April 29, 2024

The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, treatment this condition has involved the exploration immunotherapy plus as a potential approach. However, efficacy remains uncertain.

Language: Английский

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Neoadjuvant Immunotherapy: A Promising New Standard of Care

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11849 - 11849

Published: July 24, 2023

Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various malignancies, with preclinical studies showing improved immune responses preoperative setting. FDA-approved neoadjuvant-immunotherapy-based approaches include triple-negative breast cancer and early non-small cell lung on basis improvement pathological response event free survival. Nevertheless, current trials have only shown benefits fraction patients. It is therefore crucial to identify predictive biomarkers improve patient selection for such approaches. This review aims provide an overview potential neoadjuvant cancer, bladder melanoma, colorectal gastric cancer. By extrapolation metastatic setting, we explore known biomarkers, i.e., PD-L1, mismatch repair deficiency tumour mutational burden, well early-disease-specific biomarkers. We also discuss challenges identifying reliable need standardized protocols guidelines their validation clinical implementation.

Language: Английский

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Research progress on the immune microenvironment and immunotherapy in gastric cancer

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 23, 2023

The tumor microenvironment, particularly the immune plays an indispensable role in malignant progression and metastasis of gastric cancer (GC). As our understanding GC microenvironment continues to evolve, we are gaining deeper insights into biological mechanisms at single-cell level. This, turn, has offered fresh perspectives on therapy. Encouragingly, there various monotherapy combination therapies use, such as checkpoint inhibitors, adoptive cell transfer therapy, chimeric antigen receptor T antibody-drug conjugates, vaccines. In this paper, review current research progress regarding summarize promising immunotherapy targeted therapies.

Language: Английский

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Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 5, 2024

Adenocarcinoma of the esophagogastric junction (AEG) is a type tumor that arises at anatomical esophagus and stomach. Although AEG commonly classified as subtype gastric adenocarcinoma (GAC), microenvironment (TME) remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on adjacent normal tissues from four patients performed integrated analysis with publicly available GAC datasets. Our study for first time comprehensively deciphered TME landscape AEG, where heterogeneous malignant cells were identified diverse biological functions intrinsic nature. We also depicted transcriptional signatures T cell receptor (TCR) repertoires subclusters, revealing enhanced exhaustion reduced clone expansion along developmental trajectory tumor-infiltrating within AEG. Notably, observed prominent enrichment tumorigenic cancer-associated fibroblasts (CAFs) in compared to GAC. These CAFs played critical regulatory role intercellular communication network other types TME. Furthermore, accumulation might be induced by through FGF-FGFR axes. findings provide comprehensive depiction TME, which underlies potential therapeutic targets patient treatment.

Language: Английский

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Unveiling Promising Targets in Gastric Cancer Therapy: A Comprehensive Review

Deleted Journal, Journal Year: 2024, Volume and Issue: 32(3), P. 200857 - 200857

Published: Aug. 6, 2024

Gastric cancer (GC) poses a significant global health challenge, ranking fifth in incidence and third mortality among all malignancies worldwide. Its insidious onset, aggressive growth, proclivity for metastasis, limited treatment options have contributed to its high fatality rate. Traditional approaches GC primarily involve surgery chemotherapy. However, there is growing interest targeted therapies immunotherapies. This comprehensive review highlights recent advancements therapy immunotherapy. It delves into the mechanisms of various strategies, underscoring their potential treatment. Additionally, evaluates efficacy safety relevant clinical trials. Despite benefits observed numerous advanced patients with immunotherapies, challenges persist. We discuss pertinent strategies overcome these challenges, thereby providing solid foundation enhancing effectiveness

Language: Английский

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Oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab combined with nab-paclitaxel plus S-1 for gastric cancer with serosal invasion

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 25, 2024

Objective To explore the oncological outcomes of sequential laparoscopic gastrectomy after treatment with camrelizumab in combination nab-paclitaxel plus S-1 for gastric cancer serosal invasion. Methods This study is a retrospective cohort and retrospectively analyzed clinicopathological data 128 patients invasion (cT4NxM0) who received + S-1(SAP) or (C-SAP) regimen underwent laparoscopy assisted Fujian Union Hospital from March 2019 to December 2020. The were divided into SAP group C-SAP group. 2-years overall survival rate, 2-year recurrence free rate initial time compared between two groups. Results A total included, including 90 cases 38 There no significant differences age, gender, method, surgical approach, R0 resection, nerve invasion, vascular number harvested lymph nodes, positive nodes major pathologic response (MPR) groups (P>0.05). However, proportion ypT0, ypN0 pCR significantly higher than those (P<0.05). OS (80.7%) was that (67.8%), difference not statistically (P = 0.112); At 2 years operation, (44.3%) lower (55.8%) 0.097); Further analysis showed average 18.9 months, which longer 13.1 months 0.004); (P=0.076); (P= 0.097). Conclusion Camrelizumab combined neoadjuvant chemotherapy can improve patients, while prolonging group, but did increase immunotherapy/chemotherapy related side effects postoperative complications.

Language: Английский

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Evaluation of neoadjuvant immunotherapy in resectable gastric/gastroesophageal junction tumors: a meta-analysis and systematic review

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 30, 2024

Background Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy advanced has made great progress, the efficacy and safety of neoadjuvant locally have not been clearly demonstrated. Here, we conducted a systematic review meta-analysis to assess advance current research. Methods Original articles describing published up until October 15, 2023 were retrieved from PubMed, Embase, Cochrane Library, other major databases. The odds ratios (OR) 95% confidence intervals (CIs) calculated heterogeneity subgroup analysis. Results A total 1074 patients 33 studies included. effectiveness was mainly evaluated using pathological complete remission (PCR), (MPR), tumor regression grade (TRG). Among included patients, 1015 underwent surgical treatment 847 achieved R0 resection. Of treated with immunotherapy, 24% (95% CI: 19%–28%) PCR 49% 38%–61%) MPR. Safety assessed by resection rate 0.89 85%–93%), incidence ≥ 3 treatment-related adverse events (TRAEs) 28% 17%–40%), immune-related (irAEs) 19% 11%–27%). Conclusion especially dual-immunotherapy combinations, effective safe gastric/gastroesophageal in short term. Nevertheless, further multicenter randomized trials are required demonstrate which combination model more beneficial. Systematic registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358752 , identifier CRD42022358752.

Language: Английский

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Two-Year Outcomes and Biomarker Analysis of Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma After Neoadjuvant Chemotherapy and Immunotherapy from the Phase II WuhanUHGI001 Trial

Annals of Surgical Oncology, Journal Year: 2024, Volume and Issue: 31(12), P. 8157 - 8169

Published: Aug. 17, 2024

Language: Английский

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Advances in pharmacokinetics and pharmacodynamics of PD-1/PD-L1 inhibitors

International Immunopharmacology, Journal Year: 2022, Volume and Issue: 115, P. 109638 - 109638

Published: Dec. 30, 2022

Immune checkpoint inhibitors (ICIs) are a group of drugs designed to improve the therapeutic effects on various types malignant tumors. Irrespective monotherapy or combinational therapies as first-line and later-line therapy, ICIs have achieved benefits for Programmed cell death protein-1 (PD-1) / ligand 1 (PD-L1) is an immune that suppresses antitumor immunity, especially in tumor microenvironment (TME). PD-1/PD-L1 block tumor-related downregulation system, thereby enhancing immunity. In comparison with traditional small-molecule drugs, exhibit pharmacokinetic characteristics owing their high molecular weight. Furthermore, different pharmacodynamic characteristics. Hence, been approved indications by Food Drug Administration (FDA) National Medical Products (NMPA). This review summarizes studies PD-1/ PD-L1 provide reference rational clinical application.

Language: Английский

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Comparison of neoadjuvant immunotherapy versus routine neoadjuvant therapy for patients with locally advanced esophageal cancer: A systematic review and meta-analysis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 23, 2023

Background The neoadjuvant use of immune checkpoint inhibitor combined with chemotherapy (nICT) or chemoradiotherapy (nICRT) in locally advanced esophageal cancer (EC) is currently an area active ongoing research. Therefore, we carried out a comprehensive meta-analysis to compare the efficacy and safety new strategy routine strategy, which included (nCT) (nCRT). Patients methods MEDLINE (via PubMed), Embase OVID), ISI Web Science database Cochrane Library were included. And, all them searched for eligible studies between January, 2000 February, 2023. pathological complete response (pCR) major (MPR) primary outcome our study. second interest was R0 resection rate. Odds ratio (OR) associated 95% CI used as effect indicators comparing efficiency immunotherapy therapy. Fixed-effect model (Inverse Variance) random-effect (Mantel-Haenszel method) performed depending on statistically heterogeneity. Results There eight trials 652 patients meta-analysis. estimated pCR rate higher group (OR =1.86; CI, 1.25–2.75; I 2 = 32.8%, P =0.166). different results found squamous cell carcinoma (ESCC) adenocarcinoma (EAC) subgroups, OR 2.35 (95%CI, 1.00–2.72; 30.9%, =0.215) EAC subgroup, (95% 1.20–4.54; 45.3%, =0.161) ESCC respectively. also showed advantage MPR rates =2.66; 1.69–4.19; 24.3%, =0.252). no obvious difference therapy respect surgical rate, delay rate; while more treatment-related adverse events observed pneumonitis/pneumonia (OR=3.46, 1.31–9.16; 67.3%, =0.005) thyroid dysfunction (OR=4.69, 1.53–14.36; 56.5%, =0.032). Conclusion pooled correlations indicated that (both nICT nICRT) could significantly increase MPR, compared nCT nCRT) treatment EC. acceptable toxicity. However, randomized larger groups need confirm these results. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42020155802.

Language: Английский

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