{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:29:35Z","timestamp":1787164175690,"version":"build-2736575974"},"reference-count":168,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Barrett\u2019s esophagus (BE) is described by the transformation of the normal squamous epithelium into metaplastic columnar epithelium, driven by chronic gastroesophageal reflux disease (GERD). BE is a recognized premalignant condition and the main precursor to esophageal adenocarcinoma (EAC). Understanding the molecular mechanisms underlying BE carcinogenesis is crucial for improving prevention, surveillance, and treatment strategies. Methods: This narrative review examines the molecular abnormalities associated with the progression of BE to EAC. Results: This study highlights inflammatory, genetic, epigenetic, and chromosomal alterations, emphasizing key pathways and biomarkers. BE progression follows a multistep process involving dysplasia and genetic alterations such as TP53 and CDKN2A (p16) mutations, chromosomal instability, and dysregulation of pathways like PI3K\/AKT\/mTOR. Epigenetic alterations, including aberrant microRNA expression or DNA methylation, further contribute to this progression. These molecular changes are stage-specific, with some alterations occurring early in BE during the transition to high-grade dysplasia or EAC. Innovations in chemoprevention, such as combining proton pump inhibitors and aspirin, and the potential of antireflux surgery to halt disease progression are promising. Incorporating molecular biomarkers into surveillance strategies and advancing precision medicine may enable earlier detection and personalized treatments. Conclusions: BE is the primary preneoplastic condition for EAC. A deeper understanding of its molecular transformation can enhance surveillance protocols, optimize the management of gastroesophageal reflux inflammation, and refine prevention and therapeutic strategies, ultimately contributing to a reduction in the global burden of EAC.<\/jats:p>","DOI":"10.3390\/genes16030270","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T03:40:12Z","timestamp":1740454812000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular Abnormalities and Carcinogenesis in Barrett\u2019s Esophagus: Implications for Cancer Treatment and Prevention"],"prefix":"10.3390","volume":"16","author":[{"given":"Tha\u00eds Cabral","family":"de Melo Viana","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric Toshiyuki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Evidenced-Based Medicine, Centro Universit\u00e1rio Lus\u00edada, Santos 11050-071, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4666-502X","authenticated-orcid":false,"given":"Kaique Fl\u00e1vio Xavier Cardoso","family":"Filardi","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5998-7925","authenticated-orcid":false,"given":"Rodrigo Mois\u00e9s","family":"de Almeida Leite","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz Fernando Sposito Ribeiro","family":"Baltazar","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Luiz Serrano","family":"Us\u00f3n Junior","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-0496","authenticated-orcid":false,"given":"Francisco","family":"Tustumi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Universidade de Sao Paulo, Sao Paulo 05508-220, Brazil"},{"name":"Department of Health Sciences, Hospital Israelita Albert Einstein, Sao Paulo 05652-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/bjs.18003815005","article-title":"Chronic peptic ulcerz of the \u0153ophagus and \u2018\u0153sophagitis\u2019","volume":"38","author":"Barrett","year":"1950","journal-title":"Br. 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