{"doi":"10.1016/j.jcmgh.2023.02.003","title":"EGFR Reloaded: Finding New Ways to Shape Pancreatic Cancer Epigenome","abstract":"Pancreatic cancer (PC) is a devastating disease predicted to be the second leading cause of cancer deaths in approximately 15 years in the United States.1Rahib L. Wehner M.R. Matrisian L.M. et al.Estimated projection of US cancer incidence and death to 2040.JAMA Netw Open. 2021; 4e214708Crossref PubMed Scopus (354) Google Scholar With the rise of PC lethality, understanding of the mechanisms driving initiation and progression of the disease is critical to advance treatments and improve prognoses. PC has well-established highly recurrent mutations in 4 driver genes including the oncogene KRAS, and tumor suppressors TP53, CDKN2A, and SMAD4.2Maitra A. Hruban R.H. Pancreatic cancer.Annu Rev Pathol. 2008; 3: 157-188Crossref PubMed Scopus (588) Google Scholar Furthermore, different aspects of the role of the previously mentioned driver mutations on PC development have been extensively described for close to 40 years.2Maitra A. Hruban R.H. Pancreatic cancer.Annu Rev Pathol. 2008; 3: 157-188Crossref PubMed Scopus (588) Google Scholar However, these mutations alone cannot account for PC heterogeneity, discern early from advanced disease, and predict treatment response.3McDonald O.G. Li X. Saunders T. et al.Large-scale epigenomic reprogramming during pancreatic cancer progression links anabolic glucose metabolism to distant metastasis.Nat Genet. 2017; 49: 367-376Crossref PubMed Scopus (284) Google Scholar For example, 2 consensus PC subtypes with significantly different prognosis, classical and basal, are defined by differential gene expression as opposed to mutational profile.4Bailey P. Chang D.K. Nones K. et al.Genomic analyses identify molecular subtypes of pancreatic cancer.Nature. 2016; 531: 47-52Crossref PubMed Scopus (2155) Google Scholar,5Raphael B.J. Hruban R.H. Aguirre A.J. et al.Integrated genomic characterization of pancreatic ductal adenocarcinoma.Cancer Cell. 2017; 32: 185-203Abstract Full Text Full Text PDF PubMed Scopus (1071) Google Scholar Furthermore, PC metastasis is driven by enhancer reprogramming rather than secondary somatic drivers.6Roe J.-S. Hwang C.-I. Somerville T.D.D. et al.Enhancer reprogramming promotes pancreatic cancer metastasis.Cell. 2017; 170: 875-888Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar Thus, supporting the fact that key pathogenic features are largely conferred by the epigenetic make-up of PC.7Lomberk G. Blum Y. Nicolle R. et al.Distinct epigenetic landscapes underlie the pathobiology of pancreatic cancer subtypes.Nat Commun. 2018; 9: 1978Crossref PubMed Scopus (142) Google Scholar This is particularly important because the identification of epigenetic contributors to PC development is a promising field because of the relative reversible nature of epigenetic changes. In this issue of Cellular and Molecular Gastroenterology and Hepatology, Zhang et al8Zhang Z. Wang X. Hamdan F. et al.NFATc1 is a central mediator of EGFR-induced ARID1A chromatin dissociation during acinar cell reprogramming.Cell Mol Gastroenterol Hepatol. 2023; 15: 1219-1246Abstract Full Text Full Text PDF Scopus (3) Google Scholar describe a novel interplay controlling PC initiation involving the antagonism of chromatin regulator ARID1A by EGF receptor (EGFR) signaling, a well-known oncogenic cascade driving key pathways promoting PC development and progression.2Maitra A. Hruban R.H. Pancreatic cancer.Annu Rev Pathol. 2008; 3: 157-188Crossref PubMed Scopus (588) Google Scholar5Raphael B.J. Hruban R.H. Aguirre A.J. et al.Integrated genomic characterization of pancreatic ductal adenocarcinoma.Cancer Cell. 2017; 32: 185-203Abstract Full Text Full Text PDF PubMed Scopus (1071) Google Scholar The authors define a role for this interplay in modulating acinar-to-ductal metaplasia (ADM), a required initiating step of PC tumorigenesis.9Johnson B.L. d’Alincourt Salazar M. Mackenzie-Dyck S. et al.Desmoplasia and oncogene driven acinar-to-ductal metaplasia are concurrent events during acinar cell-derived pancreatic ","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2023,"id":384689,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323368,"name":"Martín E. Fernández-Zapico","orcid":"0000-0002-8089-3907","position":1,"is_corresponding":false},{"id":1152535,"name":"Kayla C. LaRue","orcid":null,"position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-19T01:17:37.110513Z","pmid":"36882150","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":[]}