Advances in Combination Therapy for Gastric Cancer: Integrating Targeted Agents and Immunotherapy
Keywords:
Gastric cancer, Combination therapy, Targeted agents, Immunotherapy, HER2, Immune checkpoint inhibitorsAbstract
Background: Despite the recent advancement in the diagnostic and therapeutic approaches, gastric cancer continues to be one of the most cardinal causes of the cancer death globally. Trends of the recent years in composite treatments that integrate biomarkers with immunotherapy along with well-tailored and individualized aggregate remedies introduce perspectives for the optimization of the outcomes.
Objective: The present review intends to qualify to give as much and more than a very comprehensive update on the latest developments of the pool of targeted agents and immunotherapy for gastric cancer, focusing on the mechanisms, medical trial effects, and future directions.
Methods: The papers for the review were identified through a comprehensive search of both PubMed as well as other databases represented in the actual journals. The filter used for search was the actual last 10 years. As for the criteria for inclusion on the studies it was only the relevance of the material, and their experience on combination remedies in gastric cancers.
Results: The combination of the former therapies, namely the human epidermal growth factor receptor 2 (HER2 inhibitors), Vascular Endothelial Growth Factor (VEGF) inhibitors, and mesenchymal-epithelial transition (MET) inhibitors has demonstrated better efficiency in various clinical trials not to mention having the right immune checkpoint inhibitors. The most important findings of current literature suggest that there is presumably cooperative interaction of all of these components, which results in more accurate anti-tumor reactions and better survival rates.
Conclusion: The inclusion of combination therapy should be highly included into recommended treatment plans for gastric cancer, especially for patients with certain molecular profiles. The evidence suggests that the combination of targeted treatment programs with immunotherapy provides significant advantages compared to typical monotherapy approaches, including increased effectiveness and improved overall survival rates.
References
[1]Alsina M, Arrazubi V, Diez M, Tabernero J. Current developments in gastric cancer: from molecular profiling to treatment strategy. Nature Reviews Gastroenterology & Hepatology. 2023, 20(3), 155-170. DOI: 10.1038/s41575-022-00703-w
[2]Balmaceda NB, Kim SS. Immunotherapy in esophagogastric cancer: Treatment landscape, challenges, and new directions. Journal of Gastrointestinal Cancer. 2024, 55(1), 153-167. DOI: 10.1007/s12029-023-01000-8
[3]Balmaceda NB, Petrillo A, Krishnan M, Zhao JJ, Kim S, et al. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society of Clinical Oncology Educational Book. 2024, 44(3), e431060. DOI: 10.1200/EDBK_431060
[4]Bardakçi M, Ergun Y. Immunotherapy in gastric cancer with liver metastasis: Challenges and opportunities. World Journal of Gastrointestinal Surgery. 2024, 16(6), 1513-1516. DOI: 10.4240/wjgs.v16.i6.1513
[5]Che G, Yin J, Wang W, Luo Y, Chen Y, et al. Circumventing drug resistance in gastric cancer: A spatial multi-omics exploration of chemo and immuno-therapeutic response dynamics. Drug Resistance Updates. 2024, 74, 101080. DOI: 10.1016/j.drup.2024.101080
[6]Chen X, Xu H, Chen X, Xu T, Tian Y, et al. First-line lambrolizumab (a PD-1 inhibitor) plus lapatinib (an VEGFR-2 inhibitor) and chemotherapy for advanced gastric cancer (SPACE): a phase 1 study. Signal Transduction and Targeted Therapy. 2024, 9(1), 73. DOI: 10.1038/s41392-024-01773-9
[7]Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives. Journal of Hematology & Oncology. 2023, 16(1), 57. DOI: 10.1186/s13045-023-01451-3
[8]He PY, Ma L, Xu B, Wang YP, Li XM, et al. Research progress and future directions of immune checkpoint inhibitor combination therapy in advanced gastric cancer. Therapeutic Advances in Medical Oncology. 2024, 16, 17588359241266156. DOI: 10.1177/17588359241266156
[9]Hu JM, Xu YH. Research Progress in Targeted Therapy for Esophageal Cancer. Journal of Biosciences and Medicines. 2024, 12(5), 77-90. DOI: 10.4236/jbm.2024.125007
[10]Jiang L, Zhao XW, Li YL, Hu YJ, Sun Y, et al. The tumor immune microenvironment remodeling and response to HER2‐targeted therapy in HER2‐positive advanced gastric cancer. IUBMB Life. 2024, 76(7), 420-436. DOI: 10.1002/iub.2804
[11]Khateeb S, Cavalcante L, Antirat N, Singh M, Sahin IH, et al. Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer? Current Treatment Options in Oncology. 2024, 25(4), 496-509. DOI: 10.1007/s11864-024-01189-1
[12]Kim IH. Emerging targets for systemic treatment of gastric cancer: HER2 and beyond. Journal of Gastric Cancer. 2024, 24(1), 29-56. DOI: 10.5230/jgc.2024.24.e6
[13]Kono K, Nakajima S, Mimura K. Biomarker-oriented chemo-immunotherapy for advanced gastric cancer. International Journal of Clinical Oncology. 2024, 29(7), 865-872. DOI: 10.1007/s10147-024-02525-z
[14]Lazăr DC, Tabun S, Corian M, Faur A, Glodis A. New advances in targeted gastric cancer treatment. World Journal of Gastroenterology. 2016, 22(30), 6776-99. DOI: 10.3748/wjg.v22.i30.6776
[15]Li H, Shen M, Wang S. Current therapies and progress in the treatment of advanced gastric cancer. Frontiers in Oncology. 2024, 14, 1327055. DOI: 10.3389/fonc.2024.1327055
[16]Liu ZX, Wang F, Zhang YQ, Lu J, Yang Y. Combination treatment with anti-HER2 therapeutic antibody RC48, PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GM-CSF) in patient with metastatic gastric cancer: a case report. Frontiers in Immunology. 2024, 15, 1321946. DOI: 10.3389/fimmu.2024.1321946
[17]Masti M, Al‐Bitran SE, Goetze TO, Thuss‐Patience P, Nordenskiöld JR, et al. Efficacy of ramucirumab combination chemotherapy as second‐line treatment in patients with advanced adenocarcinoma of the stomach or gastroesophageal junction after exposure to checkpoint inhibitors and chemotherapy as first‐line therapy. International Journal of Cancer. 2024, 154(12), 2142-2150. DOI: 10.1002/ijc.34894
[18]Narita Y, Muro K. Updated immunotherapy for gastric cancer. Journal of Clinical Medicine. 2023, 12(7), 2636. DOI: 10.3390/jcm12072636
[19]Pan D, Liu HN, Qu PF, Ma X, Ma LY, et al. Progress in the treatment of advanced hepatocellular carcinoma with immune combination therapy. World Journal of Gastrointestinal Oncology. 2024, 16(2), 273-286. DOI: 10.4251/wjgo.v16.i2.273
[20]Patel TH, Cecchini M. Targeted therapies in advanced gastric cancer. Current Treatment Options in Oncology. 2020, 21(9), 70. DOI: 10.1007/s11864-020-00774-4
[21]Pellino A, Riello E, Nappo F, Brignola S, Murdiono S, et al. Targeted therapies in metastatic gastric cancer: Current knowledge and future perspectives. World Journal of Gastroenterology. 2019, 25(38), 5773-5788. DOI: 10.3748/wjg.v25.i38.5773
[22]Pecqueux M, Fritzmann J, Adamu M, Thorlund K, Kahlert C, et al. Free intraperitoneal tumor cells and outcome in gastric cancer patients: a systematic review and meta-analysis. Oncotarget. 2015, 6(34), 35564-78. DOI: 10.18632/oncotarget.5595
[23]Rastin F, Javid H, Oryani MA, Rezagholinejad N, Afshari AR, et al. Immunotherapy for colorectal cancer: Rational strategies and novel therapeutic progress. International Immunopharmacology. 2024, 126, 111055. DOI: 10.1016/j.intimp.2023.111055
[24]Rauth S, Malafa M, Ponnusamy MP, Batra SK. Emerging Trends in Gastrointestinal Cancer Targeted Therapies: Harnessing Tumor Microenvironment, Immune Factors, and Metabolomics Insights. Gastroenterology. 2024, 167(5), 867-884. DOI: 10.1053/j.gastro.2024.05.005
[25]Scheck MK, Hofheinz RD, Lorenzen S. HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments. Cancers. 2024, 16(7), 1336. DOI: 10.3390/cancers16071336
[26]Selim JH, Shaheen S, Sheu WC, Hsueh CT. Targeted and novel therapy in advanced gastric cancer. Experimental Hematology & Oncology. 2019, 8, 25. DOI: 10.1186/s40164-019-0149-6
[27]Shi DK, Yang ZH, Cai YN, Li HB, Lin LL, et al. Research advances in the molecular classification of gastric cancer. Cellular Oncology. 2024, 47(5), 1523-1536. DOI: 10.1007/s13402-024-00951-9
[28]Kwok H H, Yang J, Lam DC. Breaking the Invisible Barriers: Unleashing the Full Potential of Immune Checkpoint Inhibitors in Oncogene-Driven Lung Adenocarcinoma. Cancers. 2023, 15(10), 2749. DOI: 10.3390/cancers15102749
[29]Sun XM, Sun FR, Zheng WW, Yu H, Liu MC, et al. Successful conversion of advanced gastric cancer treated by immunotherapy combined with chemotherapy: A case report. Cancer Advances. 2024, 7, e24008. DOI: 10.53388/2024724008
[30]Sun ZP, Zhang TJ, Ahmad MU, Zhou ZX, Qiu L, et al. Comprehensive assessment of immune context and immunotherapy response via noninvasive imaging in gastric cancer. The Journal of Clinical Investigation. 2024, 134(6), e175834. DOI: 10.1172/JCI175834
[31]Tajiri A, Nagas S, Saeed A, Saeed A. Deciphering the FGFR2 Code: Innovative Targets in Gastric Cancer Therapy. Current Oncology. 2024, 31(8), 4305-4317. DOI: 10.3390/curroncol31080321
[32]Takei S, Kawazoe A, Shitara K. The new era of immunotherapy in gastric cancer. Cancers. 2022, 14(4), 1054. DOI: 10.3390/cancers14041054
[33]Li X, Xu J, Xie J, Yang W. Research progress in targeted therapy and immunotherapy for gastric cancer. Chinese medical journal. 2022, 135(11), 1299-1313. DOI: 10.1097/CM9.0000000000002185
Zhang KQ, Xu Y, Chang XS, Xu CL, Xue WJ, et al. Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer. Cancer Immunology, Immunotherapy. 2024, 73(4), 75. DOI: 10.1007/s00262-024-03667-9
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Advances in Clinical Pharmacology and Therapeutics

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.