{"doi":"10.1016/j.jcmgh.2021.04.018","title":"Drivers of Esophageal Adenocarcinoma and Opportunities for Cancer Interception","abstract":"Barrett's esophagus (BE) is a precancerous condition that can lead to esophageal adenocarcinoma (EAC), a particularly aggressive malignancy with a low survival rate. Molecular approaches to stratifying BE risk offer intriguing opportunities for cancer interception, defined as active intervention to reduce cancer risk.1Blackburn E.H. Cancer interception.Cancer Prev Res (Phila). 2011; 4: 787-792Crossref PubMed Scopus (57) Google Scholar In the paper by Gotovac et al,2Gotovac J.R. Kader T. Milne J.V. et al.Loss of SMAD4 is sufficient to promote tumorigenesis in a model of dysplastic Barrett's esophagus.Cell Mol Gastroenterol Hepatol. 2021; 12: 689-713Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar the investigators model progression from dysplastic BE to EAC to better understand the functional significance of SMAD4 loss. Their experiments, focused on alterations in SMAD4, provide insights into how molecular alterations resulting in genomic instability can lead to rapid progression to cancer and metastasis. Detecting and understanding critical early molecular events that drive esophageal carcinogenesis may ultimately provide more effective ways to identify and treat the patients with BE at highest risk for EAC. Current BE screening and surveillance focuses clinical endoscopic resources on a subset of patients identified based on clinical risk factors for BE. Once BE is identified, long-term endoscopic surveillance of BE is recommended. However, BE is a premalignant clinical condition with low rates of progression overall.3Shaheen N.J. Falk G.W. Iyer P.G. et al.ACG clinical guideline: diagnosis and management of Barrett's esophagus.Am J Gastroenterol. 2016; 111 (quiz 51): 30-50Crossref PubMed Scopus (851) Google Scholar Indeed, a major challenge in EAC prevention is the heterogenous landscape of premalignant disease; although most cases of BE remain relatively stable over many years, others may progress rapidly or even catastrophically.4Reid B.J. Paulson T.G. Li X. Genetic insights in Barrett's esophagus and esophageal adenocarcinoma.Gastroenterology. 2015; 149: 1142-1152Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar In addition, most patients with EAC present only after the cancer has developed; 93% of patients with EAC present with advanced disease having never undergone screening or related cancer prevention strategies.5Vaughan T.L. Fitzgerald R.C. Precision prevention of oesophageal adenocarcinoma.Nat Rev Gastroenterol Hepatol. 2015; 12: 243-248Crossref PubMed Scopus (92) Google Scholar Unfortunately, the molecular mechanisms underlying progression to EAC have been difficult to discern and translate into clinical practice. In 2010, as the American Gastroenterological Association was preparing a position statement and technical review on BE, an adjunct paper by Spechler et al6Spechler S.J. Fitzgerald R.C. Prasad G.A. et al.History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus.Gastroenterology. 2010; 138: 854-869Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar noted progression of molecular events within BE. These events included early CDKN2A (P16) loss or methylation in nondysplastic BE and subsequent loss of P53 in progression to cancer.6Spechler S.J. Fitzgerald R.C. Prasad G.A. et al.History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus.Gastroenterology. 2010; 138: 854-869Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar,7Reid B.J. Prevo L.J. Galipeau P.C. et al.Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression.Am J Gastroenterol. 2001; 96: 2839-2848Crossref PubMed Google Scholar Since then, in patients with BE, CDKN2A/B loss has been identified in 88% of progressors versus 24% of nonprogressors to dysplasia and EAC.8Sepulveda J.L. Komissarova E.V. Kongkarnka S. et al.High-resolution geno","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2021,"id":224524,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9661,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":437829,"name":"Katherine S. Garman","orcid":"0000-0001-7763-8465","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":null,"created_at":"2026-07-18T23:54:18.470602Z","pmid":"34029533","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":[]}