{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:01:46Z","timestamp":1780617706546,"version":"3.54.1"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K99CA296722"],"award-info":[{"award-number":["K99CA296722"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Non\u2010small cell lung cancer (NSCLC) remains a leading cause of cancer mortality, and many patients derive limited benefit from current systemic therapies. Until now, clinical and translational efforts have largely focused on recurrent genomic alterations in the Kelch\u2010like ECH\u2010associated protein 1\u2013nuclear factor erythroid 2\u2010related factor 2 (NRF2) axis, yet mutation status alone often fails to capture the biological heterogeneity and context dependence of NRF2 pathway dysregulation. In recent years, growing evidence has highlighted the NRF2 activation state as a clinically relevant feature that better reflects resistance phenotypes and therapeutic liabilities than genotyping alone. The recent work by H\u00e4rk\u00f6nen\n                    <jats:italic>et al<\/jats:italic>\n                    , published in\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    , suggests that anchoring genotype to phenotype using functional readouts is essential for defining NRF2 hyperactivity. Mechanistic studies further suggest that NRF2 hyperactivity can impose context\u2010dependent metabolic liabilities. We discuss the next steps towards clinical translation, including prospective NRF2 activation\u2010state stratification, integration of immune context for immunotherapy, and biomarker evaluation of redox and metabolic combinations based on NRF2\u2010associated vulnerabilities. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70061","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:26:32Z","timestamp":1775564792000},"page":"265-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>NRF2<\/scp>\n                    readout beyond genotyping\n                    <sup>\u2020<\/sup>"],"prefix":"10.1002","volume":"269","author":[{"given":"Yukako","family":"Suzuki","sequence":"first","affiliation":[{"name":"Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center  Charlestown MA USA"},{"name":"Institute for Advanced Biosciences, Keio University  Tsuruoka Japan"},{"name":"Systems Biology Program, Graduate School of Media and Governance Keio University  Fujisawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8803-1463","authenticated-orcid":false,"given":"Maolin","family":"Ge","sequence":"additional","affiliation":[{"name":"Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center  Charlestown MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07943-7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.06.011"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54852-4"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.70043"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.2105"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113295"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-3848"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.01.012"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.10.002"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02103-8"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02226-6"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02598-9"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-0626"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70061","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.70061","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70061","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:12:23Z","timestamp":1780614743000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.70061"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/path.70061"],"URL":"https:\/\/doi.org\/10.1002\/path.70061","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]},"assertion":[{"value":"2026-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}