{"doi":"10.1016/j.jcmgh.2020.11.014","title":"RNF43: A Biomarker With Potential Ramifications for Therapeutic Intervention in Gastric Cancer","abstract":"Gastric adenocarcinoma is the third leading cause of cancer-related mortality worldwide and accounts for greater than 780,000 deaths annually.1Bray F. Ferlay J. Soerjomataram I. Siegel R.L. Torre L.A. Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018; 68: 394-424Crossref PubMed Scopus (50607) Google Scholar The strongest known risk factor for this malignancy is chronic gastritis induced by the bacterial pathogen Helicobacter pylori, and clinical trials have now clearly demonstrated the efficacy of H pylori eradication therapy in prevention of gastric cancer. However, most gastric cancer cases are not diagnosed until a more advanced stage, and although radiation and chemotherapy can improve outcomes, prognosis remains poor. Thus, there is a need for novel gastric cancer biomarkers to optimize the ability to improve prognostic outcomes. To date, few biomarkers associated with gastric cancer have been translated into molecularly targeted therapies. HER-2 is one such therapeutic gastric cancer biomarker.2Gravalos C. Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target.Ann Oncol. 2008; 19: 1523-1529Abstract Full Text Full Text PDF PubMed Scopus (893) Google Scholar The trastuzumab for gastric cancer study, an open-label, phase III, randomized-controlled clinical trial, investigated the efficacy of trastuzumab, a monoclonal antibody against HER-2, in combination with chemotherapy for first-line treatment of HER-2-positive gastric cancers, and revealed that trastuzumab treatment significantly improved overall survival and disease-free survival times compared with chemotherapy alone.3Bang Y.J. Van Cutsem E. Feyereislova A. Chung H.C. Shen L. Sawaki A. Lordick F. Ohtsu A. Omuro Y. Satoh T. Aprile G. Kulikov E. Hill J. Lehle M. Ruschoff J. Kang Y.K. ToGATITrastuzumab 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.Lancet. 2010; 376: 687-697Abstract Full Text Full Text PDF PubMed Scopus (5180) Google Scholar Another biomarker for gastric cancer immunotherapy is PD-L1. The ATTRACTION-2 study, a phase III, randomized, double-blind, placebo-controlled clinical trial, compared the effectiveness of nivolumab, a monoclonal antibody against PD-L1, in patients with advanced gastric cancer and revealed that nivolumab significantly increased overall survival and reduced the risk of mortality compared with placebo control subjects.4Kang Y.K. Boku N. Satoh T. Ryu M.H. Chao Y. Kato K. Chung H.C. Chen J.S. Muro K. Kang W.K. Yeh K.H. Yoshikawa T. Oh S.C. Bai L.Y. Tamura T. Lee K.W. Hamamoto Y. Kim J.G. Chin K. Oh D.Y. Minashi K. Cho J.Y. Tsuda M. Chen L.T. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet. 2017; 390: 2461-2471Abstract Full Text Full Text PDF PubMed Scopus (1333) Google Scholar However, the paucity of biomarkers that can be operationalized into actionable intervention trials is evidence of a clear gap in gastric cancer research that must be addressed. Although a brute force approach for identification of novel biomarkers has resulted in an increase in the armamentarium of potential therapeutic regimens, this is no longer considered sufficient in the design of treatment strategies. Fortunately, the molecular characterization of gastric cancers has allowed for large-scale detection of many potential biomarkers simultaneously, thus making it substantially easier to tailor specific treatment regimens to an individuals’ gastric cancer profile. The Cancer Genome Atlas analysis resulted in the identification of four different gastric cancer subtypes: (1","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2020,"id":106960,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9462,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":263097,"name":"Richard M. Peek","orcid":"0000-0002-4836-5960","position":1,"is_corresponding":false},{"id":515047,"name":"Jennifer M. Noto","orcid":"0000-0002-3497-0676","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-18T23:12:31.053776Z","pmid":"33347817","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}