Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review
Abstract
:1. Introduction
2. Epidemiology
3. Pathogenesis
4. Genetic Features
5. Clinical and Histopathological Features
6. Treatment Options and Future Direction
6.1. Chemotherapy
6.2. Immunotherapy
6.3. Target Therapies
7. Prognosis
8. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Reference | Phase | Target Population | Number of EBVaGC pts | Immunotherapy Regimen | ORR (%) | PFS (Months) | OS (Months) |
---|---|---|---|---|---|---|---|
Kim et al., 2018 [87] | II | Stage IV GOJ or GC pts treated with at least 1 line of chemotherapy and naive to anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies. | 6 | Pembrolizumab | 100.0% | 8.5 | NR |
Panda et al., 2018 [86] | I | Metastatic or locally advanced solid tumors, who failed or were not candidable to standard therapies | 1 | Avelumab | 100.0% | NR | NR |
Mishima et al., 2019 [88] | Observational | Advanced GC pts who were treated with nivolumab after two or more chemotherapy regimens | 4 | Nivolumab | 25.0% | NR | NR |
Wang et al., 2019 [89] | Ib/II | Patients with advanced GC, esophageal SCC, NPC, and head and neck SCC | 4 | Toripalimab | 25.0% | NR | NR |
Kim et al., 2020 [90] | Observational | Advanced GC patients treated with pembrolizumab or nivolumab | 4 | Nivolumab/ Pembrolizumab | 50.0% | NR | NR |
Kubota et al., 2020 [91] | Observational | Locally advanced, or metastatic GC patients treated with an anti PD-1 inhibitor after standard chemotherapies | 6 | PD-1 inhibitors | 33.3% | 3.7 | NR |
Kwon et al., 2020 [92] | Observational | Stage IV GC patients treated with PD-1 inhibitors | 7 | Nivolumab or Pembrolizumab | 42.9% | NR | NR |
Xie et al., 2020 [93] | Observational | Stage IV EBVaGC patients treated with ICIs as the first-, second-, or third-line therapy | 9 | PD-1 inhibitors, PD-1 inhibitors +XELOX, nivolumab + ipilimumab | 33.3% | NR | NR |
Sun et al., 2021 [94] | II | Metastatic or unresectable HER2-, pMMR, EBVaGC pts not previously treated with ICIs who failed or were intolerant to or prior chemotherapy | 6 | Camrelizumab | 0% | 2.2 | 6.8 |
Bai et al., 2022 [95] | Observational | Locally advanced or metastatic pMMR EBVaGC patients treated with an anti PD-1 inhibitors | 22 | PD-1/PD-L1 inhibiros (8 pts) or combination of anti-CTLA-4 plus anti-PD-1/L1 (14 pts) | 54.5% | NR | NR |
Duan et al., 2024 [96] | Observational | Metastatic GC pts who underwent various PD-1 inhibitor-based treatments as first-line therapy | 6 | PD-1 inhibitors +/−chemotherapy | NR | 17.0 | 28.0 |
Study Title (Clinical Trial Registration Number) | Phase | Target Population | Setting of Disease | Treatment Regimen | Primary End-Point | Recruitment State |
---|---|---|---|---|---|---|
Immunotherapy in MSI/dMMR Tumors in Perioperative Setting (IMHOTEP) (NCT04795661) | II | Non-metastatic, resectable-EBV+ GC, MSI/dMMR CRC, esophago-gastric cancer, endometrial carcinoma, biliary tract adc, pancreatic adc, and small bowel adc. | Localized | Pembrolizumab * | pCR | Ongoing |
D-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies (NCT03044743) | I/II | Stage IV EBV+ NPC, lymphoma or stage IV GC | Advanced stage | PD-1 knockout EBV-CTLs | Safety | Unknown |
Nanatinostat Plus Valganciclovir in Patients With Advanced EBV+ Solid Tumors, and in Combination With Pembrolizumab in EBV+ RM-NPC (NCT05166577) | Ib/II | Recurrent or metastatic EBV+ NPC (experimental choort) and advanced/metastatic EBV+ non-NPC solid tumors (exploratory proof-of-concept cohort only) | Advanced stage | Nanatinostat **+valganciclovir vs. Nanatinostat + valganciclovir + pembrolizumab ** | Safety (Ib) ORR (II) | Ongoing |
A Study to Evaluate Serplulimab in Combination with Docetaxel +S-1 VS. Docetaxel +S-1 as Adjuvant Treatment Therapy in Stage IIIc Gastric Cancer (NCT05769725) | II | PD-L1+ or MSI-H or dMMR or EBV+ GC patients | Stage IIIC | Docetaxel + S1 + Serplulimab (HLX10) * | DFS | Ongoing |
Neoadjuvant Immunotherapy and Chemotherapy for Locally Advanced Esophagogastric Junction and Gastric Cancer Trial (NICE) (NCT04744649) | II | GC patients with one of the following:
| cT3/4a Nx or T2 N+, M0 (AJCC 8th) | XELOX or SOX vs. XELOX or SOX + JS001 (toripalimab) * | MPR (residual tumor defined as less than 10%) | Ongoing |
A Phase II Study of Preoperative Pembrolizumab for Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer Followed by Chemotherapy and Chemoradiation With Pembrolizumab (NCT03257163) | II | Resectable dMMR or EBV+ GC patients | Stage Ib-IIIC | Pembrolizumab (2 cycles) followed by surgery, followed by pembrolizumab +capecitabine (5 cycles), followed by pembrolizumab (11 cycles) and radiotherapy (5 weeks). | RFS rate | Ongoing |
A Multi-center, Single-arm, Open, Phase I/IIa Clinical Trial to Evaluate the Efficacy and Safety of EBViNT Cell (EBV Specific Autologous CD8+ T Cell) in Patients With Treatment Failed Epstein Barr Virus (EBV)-Positive Malignancies (NCT03789617) | I/IIa | EBV+ Extranodal NK/T-cell lymphoma, and EBV+ GC or esophageal adenocarcinoma | Advanced stage | EBV specific autologous blood-derived T lymphocytes | Safety ORR | Ongoing |
A Study of a Selective T Cell Receptor (TCR) Targeting, Bifunctional Antibody-fusion Molecule STAR0602 in Participants With Advanced Solid Tumors (START-001) (NCT05592626) | I/II | TMB-H tumors, or MSI/dMMR tumors, or virally associated tumors, or metastatic triple negative breast cancer, or relapsed and refractory epithelial ovarian cancer, or metastatic castration-resistance prostate cancer, or KRAS wild type CRC, or KRAS mutant CRC, or stage IV NSCLC | Advanced stage | STAR0602 *** | Safety and ORR | Ongoing |
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Corallo, S.; Lasagna, A.; Filippi, B.; Alaimo, D.; Tortorella, A.; Serra, F.; Vanoli, A.; Pedrazzoli, P. Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review. Pathogens 2024, 13, 728. https://doi.org/10.3390/pathogens13090728
Corallo S, Lasagna A, Filippi B, Alaimo D, Tortorella A, Serra F, Vanoli A, Pedrazzoli P. Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review. Pathogens. 2024; 13(9):728. https://doi.org/10.3390/pathogens13090728
Chicago/Turabian StyleCorallo, Salvatore, Angioletta Lasagna, Beatrice Filippi, Domiziana Alaimo, Anna Tortorella, Francesco Serra, Alessandro Vanoli, and Paolo Pedrazzoli. 2024. "Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review" Pathogens 13, no. 9: 728. https://doi.org/10.3390/pathogens13090728