{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:48:10Z","timestamp":1792396090379,"version":"4.4.0"},"reference-count":192,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease\u2019s intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managing these innovative aspects of GC. This study aims to present an in-depth and comprehensive review of the clinical advancements in targeted therapy and immunotherapy for advanced GC.<\/jats:p>","DOI":"10.3390\/cancers15225490","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T11:31:36Z","timestamp":1700479896000},"page":"5490","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5004-9940","authenticated-orcid":false,"given":"Magdalena","family":"Sk\u00f3rzewska","sequence":"first","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Lublin, Radziwi\u0142\u0142owska 13 St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"G\u0119ca","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Lublin, Radziwi\u0142\u0142owska 13 St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6455-5636","authenticated-orcid":false,"given":"Wojciech P.","family":"Polkowski","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Medical University of Lublin, Radziwi\u0142\u0142owska 13 St., 20-080 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.3748\/wjg.v12.i3.354","article-title":"Epidemiology of gastric cancer","volume":"12","author":"Crew","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.3892\/ol.2016.4337","article-title":"Lauren classification and individualized chemotherapy in gastric cancer","volume":"11","author":"Ma","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_3","unstructured":"NcicancerStats (2023, August 23). Cancer of the Stomach\u2013Cancer Stat Facts: @NCICancerStats, Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/stomach.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1158\/1055-9965.EPI-15-0578","article-title":"Global Cancer Incidence and Mortality Rates and Trends\u2014An Update","volume":"25","author":"Torre","year":"2016","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S2468-1253(19)30328-0","article-title":"The global, regional, and national burden of stomach cancer in 195 countries, 1990\u20132017: A systematic analysis for the Global Burden of Disease study 2017","volume":"5","author":"Collaborators","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"K\u00f6rfer, J., Lordick, F., and Hacker, U.T. (2021). Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View. Cancers, 13.","DOI":"10.3390\/cancers13205216"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","article-title":"Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives","volume":"6","author":"Zhong","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13045-023-01451-3","article-title":"Gastric cancer treatment: Recent progress and future perspectives","volume":"16","author":"Guan","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_10","first-page":"1987705","article-title":"Personalized Treatment of Advanced Gastric Cancer Guided by the MiniPDX Model","volume":"2022","author":"Wang","year":"2022","journal-title":"J. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513, 202\u2013209.","DOI":"10.1038\/nature13480"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102169","DOI":"10.1016\/j.ctrv.2021.102169","article-title":"The evolving paradigm of biomarker actionability: Histology-agnosticism as a spectrum, rather than a binary quality","volume":"94","author":"Tarantino","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102019","DOI":"10.1016\/j.ctrv.2020.102019","article-title":"Review of precision cancer medicine: Evolution of the treatment paradigm","volume":"86","author":"Tsimberidou","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1158\/1078-0432.CCR-18-3694","article-title":"Agnostic-Histology Approval of New Drugs in Oncology: Are We Already There?","volume":"25","author":"Hierro","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41571-020-0384-0","article-title":"Histology-agnostic drug development\u2013considering issues beyond the tissue","volume":"17","author":"Pestana","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_16","unstructured":"Us_Fda (2023, August 23). FDA Approves Pembrolizumab for Adults and Children with TMB-H Solid Tumors|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/drug-approvals-and-databases\/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors."},{"key":"ref_17","unstructured":"Us_Fda (2023, August 23). FDA Grants Accelerated Approval to Dostarlimab-Gxly for dMMR Advanced Solid Tumors|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors."},{"key":"ref_18","unstructured":"Us_Fda (2023, August 23). FDA Grants Accelerated Approval to Pembrolizumab for First Tissue\/Site Agnostic Indication|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication."},{"key":"ref_19","unstructured":"Us_Fda (2023, August 23). FDA Approves Larotrectinib for Solid Tumors with NTRK Gene Fusions|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions-0."},{"key":"ref_20","unstructured":"Us_Fda (2023, August 23). FDA Approves Entrectinib for NTRK Solid Tumors and ROS-1 NSCLC|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-entrectinib-ntrk-solid-tumors-and-ros-1-nsclc."},{"key":"ref_21","unstructured":"Us_Fda (2023, August 23). FDA Grants Accelerated Approval to Dabrafenib in Combination with Trametinib for Unresectable or Metastatic Solid Tumors with BRAF V600E Mutation|FDA: @US_FDA, Available online: https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-grants-accelerated-approval-dabrafenib-combination-trametinib-unresectable-or-metastatic-solid."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/annonc\/mdn169","article-title":"HER2 in gastric cancer: A new prognostic factor and a novel therapeutic target","volume":"19","author":"Gravalos","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, H., Li, L., Zhang, N., Wang, Z., Xu, N., Linghu, E., and Chai, N. (2022). Relationship between HER2 overexpression and long-term outcomes of early gastric cancer: A prospective observational study with a 6-year follow-up. BMC Gastroenterol., 22.","DOI":"10.1186\/s12876-022-02309-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): A phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1126\/science.2999974","article-title":"Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene","volume":"230","author":"Coussens","year":"1985","journal-title":"Science"},{"key":"ref_26","first-page":"1525","article-title":"Cox-2 and Her2\/neu co-expression in invasive bladder cancer","volume":"26","author":"Eltze","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1080990","DOI":"10.3389\/fonc.2023.1080990","article-title":"Challenges and future of HER2-positive gastric cancer therapy","volume":"13","author":"Ma","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_28","first-page":"23","article-title":"The human epidermal growth factor receptor 2 (HER2)","volume":"50","author":"Tafe","year":"2011","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4619","DOI":"10.3748\/wjg.v22.i19.4619","article-title":"HER2 testing in gastric cancer: An update","volume":"22","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"103997","DOI":"10.1016\/j.critrevonc.2023.103997","article-title":"A review of HER2 overexpression and somatic mutations in cancers","volume":"186","author":"Galogre","year":"2023","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Iqbal, N., and Iqbal, N. (2014). Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol. Biol. Int., 2014.","DOI":"10.1155\/2014\/852748"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s10120-014-0402-y","article-title":"HER2 screening data from ToGA: Targeting HER2 in gastric and gastroesophageal junction cancer","volume":"18","author":"Bang","year":"2015","journal-title":"Gastric Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1136\/jclinpath-2012-200774","article-title":"HER2\/neu testing for anti-HER2-based therapies in patients with unresectable and\/or metastatic gastric cancer","volume":"65","author":"Garralda","year":"2012","journal-title":"J. Clin. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1093\/annonc\/mds104","article-title":"Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: A European and USA International collaborative analysis","volume":"23","author":"Janjigian","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4053","DOI":"10.1200\/jco.2004.22.90140.4053","article-title":"Expression of HER2 in gastric cancer: Comparison between protein expression and gene amplification using a new commercial kit","volume":"22","author":"Yano","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1200\/jco.2006.24.18_suppl.4089","article-title":"Correlation between HER2\/neu overexpression\/amplification and clinicopathologic parameters in advanced gastric cancer (AGC) patients (pts): A prospective study","volume":"24","author":"Gravalos","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1200\/JCO.2000.18.11.2201","article-title":"c-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems","volume":"18","author":"Allgayer","year":"2000","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1007\/s10620-005-9057-1","article-title":"HER-2\/neu amplification is an independent prognostic factor in gastric cancer","volume":"51","author":"Park","year":"2006","journal-title":"Dig. Dis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1038\/modpathol.2011.198","article-title":"HER2 testing in gastric cancer: A practical approach","volume":"25","author":"Hanna","year":"2012","journal-title":"Mod. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/modpathol.3800712","article-title":"Frequent homogeneous HER-2 amplification in primary and metastatic adenocarcinoma of the esophagus","volume":"20","author":"Reichelt","year":"2007","journal-title":"Mod. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00428-010-0952-2","article-title":"HER2 diagnostics in gastric cancer-guideline validation and development of standardized immunohistochemical testing","volume":"457","author":"Dietel","year":"2010","journal-title":"Virchows Arch."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Li, W., Zhang, X., Du, Y., Zhang, Y., Lu, J., Hu, W., and Zhao, J. (2022). HER2-targeted advanced metastatic gastric\/gastroesophageal junction adenocarcinoma: Treatment landscape and future perspectives. Biomark. Res., 10.","DOI":"10.1186\/s40364-022-00416-x"},{"key":"ref_43","first-page":"1034","article-title":"Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer","volume":"51","author":"Yonemura","year":"1991","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00280-019-03820-7","article-title":"Phase II study to evaluate the efficacy of Trastuzumab in combination with Capecitabine and Oxaliplatin in first-line treatment of HER2-positive advanced gastric cancer: HERXO trial","volume":"83","author":"Rivera","year":"2019","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.bulcan.2014.08.001","article-title":"Efficacy and safety of trastuzumab in combination with oxaliplatin and fluorouracil-based chemotherapy for patients with HER2-positive metastatic gastric and gastro-oesophageal junction adenocarcinoma patients: A retrospective study","volume":"102","author":"Soularue","year":"2015","journal-title":"Bull. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1200\/JCO.19.03077","article-title":"Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients with HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study)","volume":"38","author":"Makiyama","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1056\/NEJMoa2004413","article-title":"Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer","volume":"382","author":"Shitara","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1002\/ijc.26292","article-title":"Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes\u2014A systematic review","volume":"130","author":"Chua","year":"2012","journal-title":"Int. J. Cancer."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.21147\/j.issn.1000-9604.2020.02.05","article-title":"Evaluation of human epidermal growth factor receptor 2 status of breast cancer using preoperative multidetector computed tomography with deep learning and handcrafted radiomics features","volume":"32","author":"Yang","year":"2020","journal-title":"Chin. J. Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yang, T., Xu, R., You, J., Li, F., Yan, B., and Cheng, J.-N. (2022). Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10262-7"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1159\/000356201","article-title":"HER2 expression and PI3K-Akt pathway alterations in gastric cancer","volume":"89","author":"Sukawa","year":"2014","journal-title":"Digestion"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.5858\/arpa.2016-0331-CP","article-title":"HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology","volume":"140","author":"Bartley","year":"2016","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_53","first-page":"15","article-title":"Prospects for targeting PD-1 and PD-L1 in various tumor types","volume":"28","author":"Kim","year":"2014","journal-title":"Oncology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s13045-017-0511-2","article-title":"PD-1\/PD-L blockade in gastrointestinal cancers: Lessons learned and the road toward precision immunotherapy","volume":"10","author":"Long","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"731798","DOI":"10.3389\/fphar.2021.731798","article-title":"PD-1\/PD-L1 Checkpoint Inhibitors in Tumor Immunotherapy","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrc.2016.36","article-title":"Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy","volume":"16","author":"Topalian","year":"2016","journal-title":"Nat. Rev. Cancer."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.3389\/fimmu.2018.01474","article-title":"Biomarkers for Clinical Benefit of Immune Checkpoint Inhibitor Treatment-A Review from the Melanoma Perspective and Beyond","volume":"9","author":"Hassel","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3109\/1547691X.2012.678021","article-title":"Immunomodulating antibodies in the treatment of metastatic melanoma: The experience with anti-CTLA-4, anti-CD137, and anti-PD1","volume":"9","author":"Simeone","year":"2012","journal-title":"J. Immunotoxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/s41416-019-0515-5","article-title":"Can PD-L1 expression evaluated by biopsy sample accurately reflect its expression in the whole tumour in gastric cancer?","volume":"121","author":"Yamashita","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/j.dld.2022.01.128","article-title":"PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance. Digestive and liver disease: Official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver","volume":"54","author":"Lian","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"56","DOI":"10.5005\/jp-journals-10018-1321","article-title":"A Systematic Review and Meta-analysis of PD-1 and PD-L1 Inhibitors Monotherapy in Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma","volume":"10","author":"Voutsadakis","year":"2020","journal-title":"Euroasian J. Hepato-Gastroenterol."},{"key":"ref_62","first-page":"1115","article-title":"Optimized PD-L1 scoring of gastric cancer. Gastric cancer: Official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association","volume":"24","author":"Eschbach","year":"2021","journal-title":"Gastric Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chen, X.-J., Wei, C.-Z., Lin, J., Zhang, R.-P., Chen, G.-M., Li, Y.-F., Nie, R.-C., and Chen, Y.-M. (2023). Prognostic Significance of PD-L1 Expression in Gastric Cancer Patients with Peritoneal Metastasis. Biomedicines, 11.","DOI":"10.3390\/biomedicines11072003"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"646355","DOI":"10.3389\/fonc.2021.646355","article-title":"Appropriate PD-L1 Cutoff Value for Gastric Cancer Immunotherapy: A Systematic Review and Meta-Analysis","volume":"11","author":"Xie","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Zhai, Q., Fan, J., Lin, Q., Liu, X., Li, J., Hong, R., and Wang, S. (2019). Tumor stromal type is associated with stromal PD-L1 expression and predicts outcomes in breast cancer. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0223325"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1200\/JCO.18.00149","article-title":"Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non\u2013Small-Cell Lung Cancer with PD-L1 Tumor Proportion Score of 50% or Greater","volume":"37","author":"Reck","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"352","DOI":"10.32074\/1591-951X-803","article-title":"PD-L1 evaluation in the gastrointestinal tract: From biological rationale to its clinical application","volume":"114","author":"Mastracci","year":"2022","journal-title":"Pathologica"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.21037\/jgo-22-1133","article-title":"PD-L1 testing in advanced gastric cancer-what physicians who treat this disease must know-a literature review","volume":"14","author":"Peixoto","year":"2023","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.humpath.2007.10.024","article-title":"Gastric cancer with high-level microsatellite instability: Target gene mutations, clinicopathologic features, and long-term survival","volume":"39","author":"Falchetti","year":"2008","journal-title":"Hum. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0002-9440(10)65114-0","article-title":"Origin of microsatellite instability in gastric cancer","volume":"155","author":"Halling","year":"1999","journal-title":"Am. J. Pathol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"13320","DOI":"10.18632\/oncotarget.14519","article-title":"Programmed cell death-ligand 1 expression predicts survival in patients with gastric carcinoma with microsatellite instability","volume":"8","author":"Cho","year":"2017","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1159\/000531003","article-title":"The Day-To-Day Practice of MMR and MSI Assessment in Colorectal Adenocarcinoma: What We Know and What We Still Need to Explore","volume":"41","author":"Parente","year":"2023","journal-title":"Dig. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"305","DOI":"10.2353\/jmoldx.2006.050092","article-title":"Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers","volume":"8","author":"Murphy","year":"2006","journal-title":"J. Mol. Diagn."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.5858\/arpa.2017-0040-RA","article-title":"Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer with Microsatellite Instability? Part I-Colorectal Cancer: Microsatellite Instability, Testing, and Clinical Implications","volume":"142","author":"Marginean","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1158\/1078-0432.CCR-15-2879","article-title":"Immune and Stromal Classification of Colorectal Cancer Is Associated with Molecular Subtypes and Relevant for Precision Immunotherapy","volume":"22","author":"Becht","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12935-019-1091-8","article-title":"Microsatellite instability: A review of what the oncologist should know","volume":"20","author":"Li","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"102175","DOI":"10.1016\/j.ctrv.2021.102175","article-title":"Microsatellite instability in Gastric Cancer: Between lights and shadows","volume":"95","author":"Puliga","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lawlor, R.T., Mattiolo, P., Mafficini, A., Hong, S.-M., Piredda, M.L., Taormina, S.V., Malleo, G., Marchegiani, G., Pea, A., and Salvia, R. (2021). Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Pancreatic Cancer: Systematic Review and Still-Open Questions. Cancers, 13.","DOI":"10.3390\/cancers13133119"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1007\/s00018-018-2906-9","article-title":"Microsatellite instability in gastric cancer: Molecular bases, clinical perspectives, and new treatment approaches","volume":"75","author":"Ratti","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/JCO.19.02105","article-title":"Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability\/Mismatch Repair-Deficient Cancer: Results from the Phase II KEYNOTE-158 Study","volume":"38","author":"Marabelle","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6165","DOI":"10.1158\/1078-0432.CCR-16-2677","article-title":"Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40","volume":"23","author":"Messenheimer","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_84","unstructured":"ClinicalTrials.gov (2023, August 23). Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants with Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585\/KEYNOTE-585), Available online: https:\/\/clinicaltrials.gov\/study\/NCT03221426."},{"key":"ref_85","unstructured":"ClinicalTrials.gov (2023, August 23). Pembrolizumab\/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811\/KEYNOTE-811), Available online: https:\/\/clinicaltrials.gov\/study\/NCT03615326."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41586-021-04161-3","article-title":"The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer","volume":"600","author":"Janjigian","year":"2021","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S1470-2045(23)00515-6","article-title":"Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): A multicentre, randomised, double-blind, phase 3 trial","volume":"24","author":"Rha","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1200\/JCO.2021.39.15_suppl.2564","article-title":"Antitumor activity of dostarlimab in patients with mismatch repair-deficient\/microsatellite instability\u2013high tumors: A combined analysis of two cohorts in the GARNET study","volume":"39","author":"Andre","year":"2021","journal-title":"J. Linical Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1001\/jamaoncol.2020.4515","article-title":"Clinical Activity and Safety of the Anti\u2013Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients with Recurrent or Advanced Mismatch Repair\u2013Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial","volume":"6","author":"Oaknin","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s10120-022-01301-0","article-title":"Choice of PD-L1 immunohistochemistry assay influences clinical eligibility for gastric cancer immunotherapy. Gastric cancer: Official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association","volume":"25","author":"Lum","year":"2022","journal-title":"Gastric Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Spirina, L., Avgustinovich, A., Afanas\u2019ev, S., Volkov, M., Dobrodeev, A., Cheremisina, O., and Kostromitsky, D. (2021). PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT\/mTOR Components Change, and Autophagy Initiation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011176"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1200\/PO.20.00412","article-title":"Analytical Concordance of PD-L1 Assays Utilizing Antibodies from FDA-Approved Diagnostics in Advanced Cancers: A Systematic Literature Review","volume":"5","author":"Prince","year":"2021","journal-title":"JCO Precis. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"101925","DOI":"10.1016\/j.ctrv.2019.101925","article-title":"The evolving role of PD-L1 testing in patients with metastatic urothelial carcinoma","volume":"82","author":"Powles","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Lei, Q., Wang, D., Sun, K., Wang, L., and Zhang, Y. (2020). Resistance Mechanisms of Anti-PD1\/PDL1 Therapy in Solid Tumors. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00672"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Sun, J.Y., Zhang, D., Wu, S., Xu, M., Zhou, X., Lu, X.J., and Ji, J. (2020). Resistance to PD-1\/PD-L1 blockade cancer immunotherapy: Mechanisms, predictive factors, and future perspectives. Biomark. Res., 8.","DOI":"10.1186\/s40364-020-00212-5"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1056\/NEJMoa061884","article-title":"Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer","volume":"355","author":"Sandler","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJMoa065044","article-title":"Sunitinib versus interferon alfa in metastatic renal-cell carcinoma","volume":"356","author":"Motzer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_102","first-page":"Cd011461","article-title":"Molecular-targeted first-line therapy for advanced gastric cancer","volume":"7","author":"Song","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrclinonc.2009.110","article-title":"Targeting angiogenesis: Progress with anti-VEGF treatment with large molecules","volume":"6","author":"Grothey","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/PPO.0b013e318178d9de","article-title":"Targeting angiogenesis driven by vascular endothelial growth factors using antibody-based therapies","volume":"14","author":"Grothey","year":"2008","journal-title":"Cancer J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1200\/JCO.2005.06.081","article-title":"Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis","volume":"23","author":"Hicklin","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(13)61719-5","article-title":"Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): An international, randomised, multicentre, placebo-controlled, phase 3 trial","volume":"383","author":"Fuchs","year":"2014","journal-title":"Lancet"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1016\/S1470-2045(14)70420-6","article-title":"Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): A double-blind, randomised phase 3 trial","volume":"15","author":"Wilke","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1634\/theoncologist.2018-0602","article-title":"Initial Report of Second-Line FOLFIRI in Combination with Ramucirumab in Advanced Gastroesophageal Adenocarcinomas: A Multi-Institutional Retrospective Analysis","volume":"24","author":"Klempner","year":"2019","journal-title":"Oncologist"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"TPS4138","DOI":"10.1200\/JCO.2018.36.15_suppl.TPS4138","article-title":"An intergroup phase III trial of ramucirumab plus irinotecan in third or more line beyond progression after ramucirumab for advanced gastric cancer (RINDBeRG trial)","volume":"36","author":"Sakai","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S1470-2045(18)30791-5","article-title":"Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"20","author":"Fuchs","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/sj.bjc.6603813","article-title":"Mechanisms of adverse effects of anti-VEGF therapy for cancer","volume":"96","author":"Kamba","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"101156","DOI":"10.1016\/j.esmoop.2023.101156","article-title":"First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors","volume":"8","author":"Zheng","year":"2023","journal-title":"ESMO Open"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3389\/fonc.2020.00221","article-title":"Resistance Mechanisms to Anti-angiogenic Therapies in Cancer","volume":"10","author":"Haibe","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e000023","DOI":"10.1136\/esmoopen-2015-000023","article-title":"NTRK gene fusions as novel targets of cancer therapy across multiple tumour types","volume":"1","author":"Amatu","year":"2016","journal-title":"ESMO Open"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"103893","DOI":"10.1016\/j.amsu.2022.103893","article-title":"A review of NTRK fusions in cancer","volume":"79","author":"Manea","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41379-018-0118-3","article-title":"Molecular characterization of cancers with NTRK gene fusions","volume":"32","author":"Gatalica","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"864666","DOI":"10.3389\/fonc.2022.864666","article-title":"NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance","volume":"12","author":"Liu","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"viii16","DOI":"10.1093\/annonc\/mdz384","article-title":"Identifying patients with NTRK fusion cancer","volume":"30","author":"Solomon","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_120","unstructured":"Helwick, C. (2023, August 23). NTRK Fusions in Gastrointestinal Cancers Rare but Responsive to Treatment\u2014The ASCO Post. Available online: https:\/\/ascopost.com\/issues\/august-10-2020\/ntrk-fusions-in-gastrointestinal-cancers-rare-but-responsive-to-treatment\/."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1758835920975613","DOI":"10.1177\/1758835920975613","article-title":"A systematic review and meta-analysis of neurotrophic tyrosine receptor kinase gene fusion frequencies in solid tumors","volume":"12","author":"Forsythe","year":"2020","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_122","unstructured":"OncologyPro (2023, August 23). Epidemiology of Cancers with NTRK Gene Fusion. Available online: https:\/\/oncologypro.esmo.org\/oncology-in-practice\/anti-cancer-agents-and-biological-therapy\/targeting-ntrk-gene-fusions\/overview-of-cancers-with-ntrk-gene-fusion\/ntrk-gene-fusions-as-oncogenic-drivers\/epidemiology-of-cancers-with-ntrk-gene-fusion."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Pu, X., Fu, Y., Sun, Q., Li, L., Kwasi, A., Ma, Z., Fan, X., and Sun, B. (2023). NTRK gene alterations were enriched in hepatoid or enteroblastic differentiation type of gastric cancer. J. Clin. Pathol.","DOI":"10.2139\/ssrn.4295271"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"199","DOI":"10.32074\/1591-951X-787","article-title":"NTRK gene fusions in solid tumors: Agnostic relevance, prevalence and diagnostic strategies","volume":"114","author":"Marchetti","year":"2022","journal-title":"Pathologica"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1007\/s10120-020-01061-9","article-title":"The first case of gastric carcinoma with NTRK rearrangement: Identification of a novel ATP1B-NTRK1 fusion","volume":"23","author":"Ishikawa","year":"2020","journal-title":"Gastric Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/PO.18.00183","article-title":"Analysis of NTRK Alterations in Pan-Cancer Adult and Pediatric Malignancies: Implications for NTRK-Targeted Therapeutics","volume":"2018","author":"Okamura","year":"2018","journal-title":"JCO Precis. Oncol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s40265-018-1044-x","article-title":"Larotrectinib: First Global Approval","volume":"79","author":"Scott","year":"2019","journal-title":"Drugs"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/annonc\/mdz204","article-title":"ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research","volume":"30","author":"Scaltriti","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_129","first-page":"1","article-title":"Prevalence and clinico-genomic characteristics of patients with TRK fusion cancer in China","volume":"7","author":"Xu","year":"2023","journal-title":"npj Precis. Oncol."},{"key":"ref_130","unstructured":"OncologyPro (2023, August 23). Importance of Testing Cancers for NTRK Gene Fusions. Available online: https:\/\/oncologypro.esmo.org\/oncology-in-practice\/anti-cancer-agents-and-biological-therapy\/targeting-ntrk-gene-fusions\/importance-of-testing-cancers-for-ntrk-gene-fusions."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1056\/NEJMoa1714448","article-title":"Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children","volume":"378","author":"Drilon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S1470-2045(19)30691-6","article-title":"Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: Integrated analysis of three phase 1-2 trials","volume":"21","author":"Doebele","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"103622","DOI":"10.1016\/j.critrevonc.2022.103622","article-title":"Roles of fusion genes in digestive system cancers: Dawn for cancer precision therapy","volume":"171","author":"Zhang","year":"2022","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1090757","DOI":"10.3389\/fonc.2023.1090757","article-title":"A comprehensive overview of the relationship between RET gene and tumor occurrence","volume":"13","author":"Zhao","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"992636","DOI":"10.3389\/fonc.2022.992636","article-title":"Precision oncology for RET-related tumors","volume":"12","author":"Verrienti","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Kucharczyk, T., Krawczyk, P., Kowalski, D.M., P\u0142u\u017ca\u0144ski, A., Kubiatowski, T., and Kalinka, E. (2022). RET Proto-Oncogene-Not Such an Obvious Starting Point in Cancer Therapy. Cancers, 14.","DOI":"10.3390\/cancers14215298"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/S0168-9525(01)02420-9","article-title":"The RET receptor: Function in development and dysfunction in congenital malformation","volume":"17","author":"Santoro","year":"2001","journal-title":"Trends Genet."},{"key":"ref_138","unstructured":"Carter, D. (2023, August 23). RET inhibitors: A Treatment for Any RET-Altered Cancer: Cancerwise. Available online: https:\/\/www.mdanderson.org\/cancerwise\/ret-inhibitors--a-treatment-for-any-ret-altered-cancer.h00-159544479.html."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.trecan.2019.09.008","article-title":"Receptor Tyrosine Kinase Fusions as an Actionable Resistance Mechanism to EGFR TKIs in EGFR-Mutant Non-Small-Cell Lung Cancer","volume":"5","author":"Zhu","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"6102","DOI":"10.1158\/1078-0432.CCR-20-1587","article-title":"Progresses Toward Precision Medicine in RET-altered Solid Tumors","volume":"26","author":"Belli","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1200\/JCO.2019.37.15_suppl.3106","article-title":"The landscape of RET alterations from 56,970 adult patients with cancer: Clinical implications","volume":"37","author":"Subbiah","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1210\/er.2006-0017","article-title":"RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors","volume":"27","author":"Links","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"4536","DOI":"10.3748\/wjg.v20.i16.4536","article-title":"Targeting receptor tyrosine kinases in gastric cancer","volume":"20","author":"Morishita","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"932353","DOI":"10.3389\/fonc.2022.932353","article-title":"RET signaling pathway and RET inhibitors in human cancer","volume":"12","author":"Regua","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S1470-2045(22)00541-1","article-title":"Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): A phase 1\/2, open-label, basket trial","volume":"23","author":"Subbiah","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41591-022-01931-y","article-title":"Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1\/2 ARROW trial","volume":"28","author":"Subbiah","year":"2022","journal-title":"Nat. Med."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1158\/1078-0432.CCR-07-4790","article-title":"Advances in targeting the Ras\/Raf\/MEK\/Erk mitogen-activated protein kinase cascade with MEK inhibitors for cancer therapy","volume":"14","author":"Friday","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"ref_149","first-page":"83","article-title":"Targeting oncogenic BRAF in human cancer","volume":"355","author":"Pratilas","year":"2012","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1097\/PAI.0000000000000516","article-title":"BRAF V600E Mutation Across Multiple Tumor Types: Correlation Between DNA-based Sequencing and Mutation-specific Immunohistochemistry","volume":"26","author":"Loo","year":"2018","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/sj.bjc.6603520","article-title":"Targeting BRAF in thyroid cancer","volume":"96","author":"Espinosa","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/1476-4598-13-122","article-title":"Genetic targeting of B-RafV600E affects survival and proliferation and identifies selective agents against BRAF-mutant colorectal cancer cells","volume":"13","author":"Hirschi","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1200\/OP.21.00160","article-title":"BRAF Mutations as Actionable Targets: A Paradigm Shift in the Management of Colorectal Cancer and Novel Avenues","volume":"17","author":"Sahin","year":"2021","journal-title":"JCO Oncol. Pract."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"6942","DOI":"10.1038\/sj.onc.1206749","article-title":"BRAF and KRAS mutations in stomach cancer","volume":"22","author":"Lee","year":"2003","journal-title":"Oncogene"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1016\/S1470-2045(20)30321-1","article-title":"Dabrafenib plus trametinib in patients with BRAF(V600E)-mutated biliary tract cancer (ROAR): A phase 2, open-label, single-arm, multicentre basket trial","volume":"21","author":"Subbiah","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3895","DOI":"10.1200\/JCO.20.00762","article-title":"Dabrafenib and Trametinib in Patients with Tumors with BRAF(V600E) Mutations: Results of the NCI-MATCH Trial Subprotocol H","volume":"38","author":"Salama","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e404770","DOI":"10.1200\/EDBK_404770","article-title":"Expanding the Benefit: Dabrafenib\/Trametinib as Tissue-Agnostic Therapy for BRAF V600E\u2013Positive Adult and Pediatric Solid Tumors","volume":"43","author":"Gouda","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"King, A.J., Arnone, M.R., Bleam, M.R., Moss, K.G., Yang, J., Fedorowicz, K.E., Smitheman, K.N., Erhardt, J.A., Hughes-Earle, A., and Kane-Carson, L.S. (2013). Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF\/MEK tool combination reduced skin lesions. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067583"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1056\/NEJMoa1406037","article-title":"Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma","volume":"371","author":"Long","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/S1470-2045(16)30146-2","article-title":"Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: An open-label, multicentre phase 2 trial","volume":"17","author":"Planchard","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1200\/JCO.2017.73.6785","article-title":"Dabrafenib and Trametinib Treatment in Patients with Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer","volume":"36","author":"Subbiah","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1158\/1535-7163.MCT-21-0950","article-title":"Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600-Mutant Tumors","volume":"21","author":"Adashek","year":"2022","journal-title":"Mol. Cancer Ther."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41591-023-02321-8","article-title":"Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: The phase 2 ROAR trial","volume":"29","author":"Subbiah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"4105615","DOI":"10.1155\/2016\/4105615","article-title":"Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application","volume":"2016","author":"Li","year":"2016","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejca.2022.10.004","article-title":"KN026 (anti-HER2 bispecific antibody) in patients with previously treated, advanced HER2-expressing gastric or gastroesophageal junction cancer","volume":"178","author":"Xu","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/S1470-2045(17)30111-0","article-title":"Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): An international randomised, open-label, adaptive, phase 2\/3 study","volume":"18","author":"Shah","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1470-2045(23)00108-0","article-title":"Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): A global, randomised, placebo-controlled, phase 3 study","volume":"24","author":"Xu","year":"2023","journal-title":"Lancet Oncol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s10120-022-01335-4","article-title":"Pertuzumab, trastuzumab, and chemotherapy in HER2-positive gastric\/gastroesophageal junction cancer: End-of-study analysis of the JACOB phase III randomized clinical trial","volume":"26","author":"Tabernero","year":"2023","journal-title":"Gastric Cancer"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"S1102","DOI":"10.1016\/j.annonc.2022.07.1328","article-title":"1210P The preliminary efficacy and safety of KN026 combined with KN046 treatment in HER2-positive locally advanced unresectable or metastatic gastric\/gastroesophageal junction cancer without prior systemic treatment in a phase II study","volume":"33","author":"Shen","year":"2022","journal-title":"Ann. Oncol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1158\/1078-0432.CCR-21-2827","article-title":"First-in-human HER2-targeted Bispecific Antibody KN026 for the Treatment of Patients with HER2-positive Metastatic Breast Cancer: Results from a Phase I Study","volume":"28","author":"Zhang","year":"2022","journal-title":"Clin. Cancer Res."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1200\/JCO.2023.41.16_suppl.3621","article-title":"Efficacy and safety of KN026 in combination with KN046 in patients with locally advanced unresectable or metastatic HER2-positive other solid tumors","volume":"41","author":"Gong","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/cac2.12214","article-title":"Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: A single-arm phase II study","volume":"41","author":"Peng","year":"2021","journal-title":"Cancer Commun."},{"key":"ref_173","first-page":"31","article-title":"Abstract 31: Preclinical development of a novel biparatopic HER2 antibody with activity in low to high HER2 expressing cancers","volume":"77","author":"Weisser","year":"2023","journal-title":"Cancer Res. Am. Assoc. Cancer Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1200\/JCO.2023.41.4_suppl.347","article-title":"Zanidatamab + chemotherapy as first-line treatment for HER2-expressing metastatic gastroesophageal adenocarcinoma (mGEA)","volume":"41","author":"Elimova","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1200\/JCO.2023.41.4_suppl.286","article-title":"Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC\/GEJC)","volume":"41","author":"Moehler","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"736955","DOI":"10.3389\/fonc.2021.736955","article-title":"Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer","volume":"11","author":"Lou","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"2014296","DOI":"10.1080\/19420862.2021.2014296","article-title":"Antibodies to watch in 2022","volume":"14","author":"Kaplon","year":"2022","journal-title":"MAbs"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Lee, K.-W., Chung, H., Kim, T.M., Lakhani, N., Messersmith, W., Santana-Davila, R., Kim, W.S., LoRusso, P., Bang, Y.J., and Chow, L. (2021). 498 Evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) and with gastric\/gastroesophageal cancer (GC); ASPEN-01. J. ImmunoTherapy Cancer, 9.","DOI":"10.1136\/jitc-2021-SITC2021.498"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"CT078","DOI":"10.1158\/1538-7445.AM2023-CT078","article-title":"Abstract CT078: First-line treatment with sintilimab (sin) vs placebo in combination with chemotherapy (chemo) in patients (pts) with unresectable gastric or gastroesophageal junction (G\/GEJ) cancer: Final overall survival (OS) results from the randomized, phase III ORIENT-16 trial","volume":"83","author":"Xu","year":"2023","journal-title":"Cancer Res."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"759","DOI":"10.2217\/imt-2019-0011","article-title":"Avelumab in Gastric Cancer","volume":"11","author":"Sobhani","year":"2019","journal-title":"Immunotherapy"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1093\/annonc\/mdy264","article-title":"Phase III, randomised trial of avelumab versus physician\u2019s choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: Primary analysis of JAVELIN Gastric 300","volume":"29","author":"Bang","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1200\/JCO.20.00892","article-title":"Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients with Gastric Cancers: Results from JAVELIN Gastric 100","volume":"39","author":"Moehler","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_183","unstructured":"(2023, August 23). Domvanalimab|Anti-TIGIT Candidate|Arcus Biosciences. Available online: https:\/\/arcusbio.com\/our-science\/clinical-candidates\/anti-tigit-antibodies\/domvanalimab\/."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.2217\/fon-2019-0141","article-title":"Bemarituzumab with modified FOLFOX6 for advanced FGFR2-positive gastroesophageal cancer: FIGHT Phase III study design","volume":"15","author":"Catenacci","year":"2019","journal-title":"Future Oncol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1200\/JCO.19.01834","article-title":"Phase I Escalation and Expansion Study of Bemarituzumab (FPA144) in Patients with Advanced Solid Tumors and FGFR2b-Selected Gastroesophageal Adenocarcinoma","volume":"38","author":"Catenacci","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1074\/jbc.M210665200","article-title":"The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity","volume":"278","author":"Shinkawa","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1016\/S1470-2045(22)00603-9","article-title":"Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): A randomised, double-blind, placebo-controlled, phase 2 study","volume":"23","author":"Wainberg","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"TPS4164","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS4164","article-title":"Trial in progress: Phase 3 study of bemarituzumab + mFOLFOX6 versus placebo + mFOLFOX6 in previously untreated advanced gastric or gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-101)","volume":"40","author":"Smyth","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_189","unstructured":"(2023, October 03). ALX Oncology Reports Positive Interim Phase 2 ASPEN-06: Globenewswire. Available online: https:\/\/www.globenewswire.com\/news-release\/2023\/10\/03\/2753394\/0\/en\/ALX-Oncology-Reports-Positive-Interim-Phase-2-ASPEN-06-Clinical-Trial-Results-of-Evorpacept-for-the-Treatment-of-Advanced-HER2-Positive-Gastric-Cancer.html."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1038\/s41591-023-02465-7","article-title":"Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: The randomized, phase 3 GLOW trial","volume":"29","author":"Shah","year":"2023","journal-title":"Nat. Med."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"e001279","DOI":"10.1136\/jitc-2020-001279","article-title":"HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: A multicenter, single-arm phase II trial","volume":"8","author":"Song","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_192","unstructured":"(2023, August 23). Ipilimumab and Oxaliplatin and Capecitabine in Gastric Cancer-Clinical Trials Registry-ICH GCP. Available online: https:\/\/ichgcp.net\/clinical-trials-registry\/NCT05144854."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5490\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:26:31Z","timestamp":1760131591000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/22\/5490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,20]]},"references-count":192,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cancers15225490"],"URL":"https:\/\/doi.org\/10.3390\/cancers15225490","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,20]]}}}