{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:37:38Z","timestamp":1777081058789,"version":"3.51.4"},"reference-count":239,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01 CA244236"],"award-info":[{"award-number":["R01 CA244236"]}]},{"name":"National Institutes of Health","award":["AA030026"],"award-info":[{"award-number":["AA030026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The lethality of esophageal squamous cell carcinoma (ESCC), and other epithelial cancers, is primarily due to its aggressive nature and frequent lymphatic metastasis, both of which impact prognosis. In this review, we explore the underlying molecular mechanisms of ESCC lymphatic metastasis, specifically, the functional role of NRF2 and therapeutic strategies. Current data suggest that NRF2 hyperactivation (NRF2high) may promote lymphatic metastasis of ESCC by affecting the extracellular matrix (ECM), epithelial\u2013mesenchymal transition (EMT), lymphangiogenesis, immune evasion, metabolic programming, and Hippo signaling. We also update the latest developments in NRF2 inhibitors, their mechanisms of action, screening strategies, and approaches for evaluating compound efficacy. Finally, we highlight the utility of animal models for mechanistic studies and therapeutic development. We believe elucidation of the functional role of NRF2 in ESCC lymphatic metastasis and developing proper NRF2 inhibitors will greatly improve the clinical prognosis of ESCC in human patients.<\/jats:p>","DOI":"10.3390\/cancers17111853","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:09:12Z","timestamp":1748840952000},"page":"1853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies"],"prefix":"10.3390","volume":"17","author":[{"given":"Yahui","family":"Li","sequence":"first","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Ladd","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"},{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhaohui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice","family":"Bui-Linh","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chorlada","family":"Paiboonrungruang","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0243-3777","authenticated-orcid":false,"given":"Boopathi","family":"Subramaniyan","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haining","family":"Wang","sequence":"additional","affiliation":[{"name":"Insilico Medicine Canada Inc., Montreal, QC H3B 4W8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Curt","family":"Balch","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David D.","family":"Shersher","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"},{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"},{"name":"MD Anderson Cancer Center at Cooper, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Spitz","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"},{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"},{"name":"MD Anderson Cancer Center at Cooper, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Surgical Research Lab, Department of Surgery, Cooper University Health Care, Camden, NJ 08103, USA"},{"name":"Cooper Medical School of Rowan University, Camden, NJ 08103, USA"},{"name":"Coriell Institute for Medical Research, Camden, NJ 08103, USA"},{"name":"MD Anderson Cancer Center at Cooper, Camden, NJ 08103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7648","DOI":"10.3748\/wjg.v21.i25.7648","article-title":"Personalized targeted therapy for esophageal squamous cell carcinoma","volume":"21","author":"Kang","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41571-023-00757-y","article-title":"Improving outcomes in patients with oesophageal cancer","volume":"20","author":"Shah","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.ejso.2011.06.018","article-title":"Lymph node metastases and prognosis in oesophageal carcinoma\u2014A systematic review","volume":"37","author":"Kayani","year":"2011","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s00508-012-0310-2","article-title":"Prognostic significance of lymph node characteristics on survival in esophageal squamous cell carcinomas","volume":"125","author":"Wu","year":"2013","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jss.2023.07.027","article-title":"The Prognostic Significance of Lymph Node Ratio for Esophageal Cancer: A Meta-Analysis","volume":"292","author":"Song","year":"2023","journal-title":"J. Surg. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e34189","DOI":"10.1097\/MD.0000000000034189","article-title":"Nomogram for predicting survival after lymphatic metastasis in esophageal cancer: A SEER analysis","volume":"102","author":"Sun","year":"2023","journal-title":"Medicine"},{"key":"ref_8","unstructured":"American Cancer Society (2025, May 23). Survival Rates for Esophageal Cancer. Available online: https:\/\/www.cancer.org\/cancer\/types\/esophagus-cancer\/detection-diagnosis-staging\/survival-rates.html."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1172\/JCI71606","article-title":"Mechanisms of lymphatic metastasis","volume":"124","author":"Karaman","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10388-018-0642-8","article-title":"Esophageal cancer practice guidelines 2017 edited by the Japan esophageal society: Part 2","volume":"16","author":"Kitagawa","year":"2019","journal-title":"Esophagus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s40792-016-0271-1","article-title":"Distant lymph node metastases caused by esophageal cancer invasion to the lamina propria: A case report","volume":"2","author":"Tsutsumi","year":"2016","journal-title":"Surg. Case Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jones, D., Pereira, E.R., and Padera, T.P. (2018). Growth and immune evasion of lymph node metastasis. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00036"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1126\/science.aay4509","article-title":"Stem cell-driven lymphatic remodeling coordinates tissue regeneration","volume":"366","author":"Yang","year":"2019","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"90","DOI":"10.4240\/wjgs.v8.i1.90","article-title":"Lymphatic spreading and lymphadenectomy for esophageal carcinoma","volume":"8","author":"Ji","year":"2016","journal-title":"World J. Gastrointest. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/S0022-5223(03)00036-9","article-title":"Submucosal territory of the direct lymphatic drainage system to the thoracic duct in the human esophagus","volume":"125","author":"Kuge","year":"2003","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S724","DOI":"10.21037\/jtd.2017.06.19","article-title":"Pattern of lymph node metastases of squamous cell esophageal cancer based on the anatomical lymphatic drainage system: Efficacy of lymph node dissection according to tumor location","volume":"9","author":"Tachimori","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.2147\/CMAR.S182436","article-title":"Anatomy of lymphatic drainage of the esophagus and lymph node metastasis of thoracic esophageal cancer","volume":"10","author":"Wang","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1139","DOI":"10.1097\/MD.0000000000001139","article-title":"Retrograde Lymphatic Spread of Esophageal Cancer: A Case Report","volume":"94","author":"Oshiro","year":"2015","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1245\/s10434-020-09509-z","article-title":"Prognostic Role of Nodal Skip Metastasis in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Multicenter Study","volume":"28","author":"Shang","year":"2021","journal-title":"Ann. Surg. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1586\/egh.11.33","article-title":"Risk of lymph node metastasis in submucosal esophageal cancer: A review of surgically resected patients","volume":"5","author":"Gockel","year":"2011","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1007\/s00268-011-1143-2","article-title":"Lymphatic tumor emboli detected by D2-40 immunostaining can more accurately predict lymph-node metastasis","volume":"35","author":"Moriya","year":"2011","journal-title":"World J. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s13019-020-01302-z","article-title":"Lymph node metastatic patterns and its clinical significance for thoracic superficial esophageal squamous cell carcinoma","volume":"15","author":"Wang","year":"2020","journal-title":"J. Cardiothorac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"523","DOI":"10.5946\/ce.2014.47.6.523","article-title":"Lymph node metastases in esophageal carcinoma: An endoscopist\u2019s view","volume":"47","author":"Cho","year":"2014","journal-title":"Clin. Endosc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"15819","DOI":"10.1007\/s00432-023-05359-w","article-title":"Precise pattern of lymphatic spread of esophageal squamous cell carcinoma: Results of 1074 patients with N1 disease","volume":"149","author":"Lin","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_25","first-page":"127","article-title":"Sentinel lymph node in oesophageal cancer-a systematic review and meta-analysis","volume":"5","author":"Nagaraja","year":"2014","journal-title":"J. Gastrointest. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Duan, X., Shang, X., Yue, J., Ma, Z., Chen, C., Tang, P., Jiang, H., and Yu, Z. (2021). A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma. BMC Cancer, 21.","DOI":"10.1186\/s12885-021-08077-z"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.jtcvs.2013.07.006","article-title":"Prevalence of lymph node metastases in superficial esophageal squamous cell carcinoma","volume":"146","author":"Li","year":"2013","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.21037\/jtd.2018.06.51","article-title":"A nomogram for predicting lymph node metastasis in surgically resected T1 esophageal squamous cell carcinoma","volume":"10","author":"Shen","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/j.jtcvs.2017.11.005","article-title":"A prediction model for lymph node metastasis in T1 esophageal squamous cell carcinoma","volume":"155","author":"Wu","year":"2018","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s10620-022-07586-6","article-title":"Lymphatic Drainage System and Lymphatic Metastasis of Cancer Cells in the Mouse Esophagus","volume":"68","author":"Li","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.semcdb.2014.10.002","article-title":"Sentinel lymph node metastases in cancer: Causes, detection and their role in disease progression","volume":"38","author":"Nathanson","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.jtcvs.2009.07.017","article-title":"Determination of the minimum number of lymph nodes to examine to maximize survival in patients with esophageal carcinoma: Data from the Surveillance Epidemiology and End Results database","volume":"139","author":"Groth","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1097\/SLA.0000000000005627","article-title":"Ten-Year Survival and Recurrence Patterns After Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus","volume":"278","author":"Altorki","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e772","DOI":"10.1097\/SLA.0000000000005197","article-title":"Extended Lymphadenectomy Improves Survival After Induction Chemoradiation for Esophageal Cancer: A Propensity-Matched Analysis of the National Cancer Database","volume":"277","author":"Kamel","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000226971","article-title":"Results of a nationwide study on the three-field lymph node dissection of esophageal cancer","volume":"48","author":"Isono","year":"1991","journal-title":"Oncology"},{"key":"ref_36","first-page":"djv043","article-title":"Extent of lymph node removal during esophageal cancer surgery and survival","volume":"107","author":"Johar","year":"2015","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jtho.2020.10.157","article-title":"Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial","volume":"16","author":"Li","year":"2021","journal-title":"J. Thorac. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"doad006","DOI":"10.1093\/dote\/doad006","article-title":"Lymph node metastatic patterns and the development of multidisciplinary treatment for esophageal cancer","volume":"36","author":"Matsuda","year":"2023","journal-title":"Dis. Esophagus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the Hallmarks of Cancer","volume":"34","author":"Chapman","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.2337\/db22-0623","article-title":"NRF2 and Diabetes: The Good, the Bad, and the Complex","volume":"71","author":"Dodson","year":"2022","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110105","DOI":"10.1016\/j.cellsig.2021.110105","article-title":"Development of targeted therapy of NRF2high esophageal squamous cell carcinoma","volume":"86","author":"Paiboonrungruang","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1101\/gad.225680.113","article-title":"The emerging role of the Nrf2-Keap1 signaling pathway in cancer","volume":"27","author":"Jaramillo","year":"2013","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 System: A Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature, 541, 169\u2013175.","DOI":"10.1038\/nature20805"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Hirose, W., Oshikiri, H., Taguchi, K., and Yamamoto, M. (2022). The KEAP1-NRF2 System and Esophageal Cancer. Cancers, 14.","DOI":"10.3390\/cancers14194702"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1158\/0008-5472.CAN-18-2723","article-title":"NRF2 Activation in Cancer: From DNA to Protein","volume":"79","author":"Cloer","year":"2019","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.1038\/s41467-022-32962-1","article-title":"Integrated cohort of esophageal squamous cell cancer reveals genomic features underlying clinical characteristics","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4034","DOI":"10.1111\/cas.16355","article-title":"Specific cancer types and prognosis in patients with variations in the KEAP1-NRF2 system: A retrospective cohort study","volume":"115","author":"Iwasaki","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1245\/s10434-014-3600-2","article-title":"Nrf2 is useful for predicting the effect of chemoradiation therapy on esophageal squamous cell carcinoma","volume":"21","author":"Kawasaki","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1593\/neo.11750","article-title":"NRF2 mutation confers malignant potential and resistance to chemoradiation therapy in advanced esophageal squamous cancer","volume":"13","author":"Shibata","year":"2011","journal-title":"Neoplasia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1038\/s41379-022-01010-0","article-title":"High expression of nuclear NRF2 combined with NFE2L2 alterations predicts poor prognosis in esophageal squamous cell carcinoma patients","volume":"35","author":"Jiang","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Tamborero, D., Gonzalez-Perez, A., Perez-Llamas, C., Deu-Pons, J., Kandoth, C., Reimand, J., Lawrence, M.S., Getz, G., Bader, G.D., and Ding, L. (2013). Comprehensive identification of mutational cancer driver genes across 12 tumor types. Sci. Rep., 3.","DOI":"10.1038\/srep02952"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/nyas.13681","article-title":"Targeted therapy of esophageal squamous cell carcinoma: The NRF2 signaling pathway as target","volume":"1434","author":"Ma","year":"2018","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ccell.2022.12.004","article-title":"Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma","volume":"41","author":"Liu","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.cell.2019.06.003","article-title":"Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1","volume":"178","author":"Lignitto","year":"2019","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature15726","article-title":"Oxidative stress inhibits distant metastasis by human melanoma cells","volume":"527","author":"Piskounova","year":"2015","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.cell.2019.06.005","article-title":"BACH1 stabilization by antioxidants stimulates lung cancer metastasis","volume":"178","author":"Wiel","year":"2019","journal-title":"Cell"},{"key":"ref_58","first-page":"334ra51","article-title":"NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis","volume":"8","author":"Wang","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1158\/1078-0432.CCR-22-2747","article-title":"Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma","volume":"29","author":"Osman","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1111\/jcmm.14241","article-title":"Nrf2 promotes breast cancer cell migration via up-regulation of G6PD\/HIF-1alpha\/Notch1 axis","volume":"23","author":"Zhang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ccell.2019.12.012","article-title":"Dynamic ROS Control by TIGAR Regulates the Initiation and Progression of Pancreatic Cancer","volume":"37","author":"Cheung","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41556-025-01617-w","article-title":"Intratumour oxidative hotspots provide a niche for cancer cell dissemination","volume":"27","author":"Ueda","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1093\/carcin\/bgq105","article-title":"Nrf2-deficiency creates a responsive microenvironment for metastasis to the lung","volume":"31","author":"Satoh","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1158\/1940-6207.CAPR-14-0094","article-title":"Myeloid lineage-specific deletion of antioxidant system enhances tumor metastasis","volume":"7","author":"Hiramoto","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"25ra23","DOI":"10.1126\/scitranslmed.3000403","article-title":"Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer","volume":"2","author":"Stott","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41568-019-0221-x","article-title":"Fluids and their mechanics in tumour transit: Shaping metastasis","volume":"20","author":"Follain","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1158\/0008-5472.CAN-10-4455","article-title":"Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis","volume":"71","author":"Hood","year":"2011","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1002\/ijc.26027","article-title":"Do all roads lead to Rome? Routes to metastasis development","volume":"128","author":"Sleeman","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8065","DOI":"10.1158\/0008-5472.CAN-06-1392","article-title":"Imaging steps of lymphatic metastasis reveals that vascular endothelial growth factor-C increases metastasis by increasing delivery of cancer cells to lymph nodes: Therapeutic implications","volume":"66","author":"Hoshida","year":"2006","journal-title":"Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1182\/blood-2006-05-021758","article-title":"VEGF-C\u2013induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites","volume":"109","author":"Hirakawa","year":"2007","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.devcel.2019.03.026","article-title":"The extracellular matrix modulates the metastatic journey","volume":"49","author":"Kai","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41568-018-0038-z","article-title":"Every step of the way: Integrins in cancer progression and metastasis","volume":"18","author":"Hamidi","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/nature07275","article-title":"A paracrine requirement for hedgehog signalling in cancer","volume":"455","author":"Yauch","year":"2008","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cell.2016.06.028","article-title":"EMT: 2016","volume":"166","author":"Nieto","year":"2016","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/s41568-020-00320-2","article-title":"The metabolism of cancer cells during metastasis","volume":"21","author":"Bergers","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s43018-020-0088-5","article-title":"The current paradigm and challenges ahead for the dormancy of disseminated tumor cells","volume":"1","author":"Risson","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1126\/science.aal3662","article-title":"Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice","volume":"359","author":"Brown","year":"2018","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1126\/science.aal3622","article-title":"Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice","volume":"359","author":"Pereira","year":"2018","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/10739680600893909","article-title":"Lymph flow, shear stress, and lymphocyte velocity in rat mesenteric prenodal lymphatics","volume":"13","author":"Dixon","year":"2006","journal-title":"Microcirculation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41586-020-2623-z","article-title":"Lymph protects metastasizing melanoma cells from ferroptosis","volume":"585","author":"Ubellacker","year":"2020","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lin, S., Chen, Y., Wang, J., Cai, Y., Chen, X., Chen, Y., Shi, Y., Chen, G., and Zhu, K. (2022). Multi-Region Genomic Landscape Analysis for the Preoperative Prediction of Lymph Node Metastasis in Esophageal Carcinoma. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.830601"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1038\/s41467-021-24813-2","article-title":"Oncogenic enhancers drive esophageal squamous cell carcinogenesis and metastasis","volume":"12","author":"Ye","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e2204565","DOI":"10.1002\/advs.202204565","article-title":"Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Esophageal Squamous Cell Carcinoma","volume":"10","author":"Jia","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"780","DOI":"10.2337\/db15-0564","article-title":"An Essential Role of NRF2 in Diabetic Wound Healing","volume":"65","author":"Long","year":"2016","journal-title":"Diabetes"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9095","DOI":"10.1158\/0008-5472.CAN-10-0384","article-title":"Global downstream pathway analysis reveals a dependence of oncogenic NF-E2-related factor 2 mutation on the mTOR growth signaling pathway","volume":"70","author":"Shibata","year":"2010","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1042\/BJ20111648","article-title":"Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation","volume":"443","author":"Xue","year":"2012","journal-title":"Biochem. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1186\/s12967-023-04287-0","article-title":"The promoting effect and mechanism of Nrf2 on cell metastasis in cervical cancer","volume":"21","author":"Zhang","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/intbio\/zyz021","article-title":"NRF2 activates a partial epithelial-mesenchymal transition and is maximally present in a hybrid epithelial\/mesenchymal phenotype","volume":"11","author":"Bocci","year":"2019","journal-title":"Integr. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Vilchez Mercedes, S.A., Bocci, F., Ahmed, M., Eder, I., Zhu, N., Levine, H., Onuchic, J.N., Jolly, M.K., and Wong, P.K. (2022). Nrf2 modulates the hybrid epithelial\/mesenchymal phenotype and Notch signaling during collective cancer migration. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.807324"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"73593","DOI":"10.18632\/oncotarget.12435","article-title":"NRF2 promotes breast cancer cell proliferation and metastasis by increasing RhoA\/ROCK pathway signal transduction","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1186\/s12935-021-02184-4","article-title":"Nestin is essential for cellular redox homeostasis and gastric cancer metastasis through the mediation of the Keap1-Nrf2 axis","volume":"21","author":"Lv","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13046-019-1135-x","article-title":"MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS\/Nrf2\/Notch pathway in hepatocellular carcinoma","volume":"38","author":"Jin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"20009","DOI":"10.1073\/pnas.1013805107","article-title":"Autocrine TGF-\u03b2 and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts","volume":"107","author":"Kojima","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Kang, J.I., Kim, D.H., Sung, K.W., Shim, S.M., Cha-Molstad, H., Soung, N.K., Lee, K.H., Hwang, J., Lee, H.G., and Kwon, Y.T. (2021). p62-induced cancer-associated fibroblast activation via the Nrf2-ATF6 pathway promotes lung tumorigenesis. Cancers, 13.","DOI":"10.3390\/cancers13040864"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Li, Y.-L., and Hung, W.-C. (2022). Reprogramming of sentinel lymph node microenvironment during tumor metastasis. J. Biomed. Sci., 29.","DOI":"10.1186\/s12929-022-00868-1"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"102247","DOI":"10.1016\/j.coi.2022.102247","article-title":"Regulation of innate immunity by Nrf2","volume":"78","author":"Laguette","year":"2022","journal-title":"Curr. Opin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/carcin\/bgaa039","article-title":"NRF2 as a regulator of cell metabolism and inflammation in cancer","volume":"41","author":"He","year":"2020","journal-title":"Carcinogenesis"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cell.2021.12.005","article-title":"EMSY inhibits homologous recombination repair and the interferon response, promoting lung cancer immune evasion","volume":"185","author":"Marzio","year":"2022","journal-title":"Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1038\/s41467-018-05861-7","article-title":"Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming","volume":"9","author":"Olagnier","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Harkonen, J., Polonen, P., Deen, A.J., Selvarajan, I., Teppo, H.R., Dimova, E.Y., Kietzmann, T., Ahtiainen, M., Vayrynen, J.P., and Vayrynen, S.A. (2023). A pan-cancer analysis shows immunoevasive characteristics in NRF2 hyperactive squamous malignancies. Redox Biol., 61.","DOI":"10.1016\/j.redox.2023.102644"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4941","DOI":"10.1038\/s41388-018-0314-0","article-title":"Targeting the upstream transcriptional activator of PD-L1 as an alternative strategy in melanoma therapy","volume":"37","author":"Zhu","year":"2018","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"774","DOI":"10.2353\/ajpath.2007.060761","article-title":"Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis","volume":"170","author":"Harrell","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"H709","DOI":"10.1152\/ajpheart.00102.2007","article-title":"Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism","volume":"293","author":"Breslin","year":"2007","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1158\/0008-5472.CAN-10-3007","article-title":"NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1alpha","volume":"71","author":"Kim","year":"2011","journal-title":"Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"E3910","DOI":"10.1073\/pnas.1309276110","article-title":"Nrf2 acts cell-autonomously in endothelium to regulate tip cell formation and vascular branching","volume":"110","author":"Wei","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"ra52","DOI":"10.1126\/scisignal.2000762","article-title":"Regulation of notch1 signaling by nrf2: Implications for tissue regeneration","volume":"3","author":"Wakabayashi","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1093\/nar\/gkq212","article-title":"Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis","volume":"38","author":"Malhotra","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e202000666","DOI":"10.26508\/lsa.202000666","article-title":"BACH family members regulate angiogenesis and lymphangiogenesis by modulating VEGFC expression","volume":"3","author":"Cohen","year":"2020","journal-title":"Life Sci. Alliance"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1038\/s41388-020-01432-7","article-title":"Metabolic rewiring in the promotion of cancer metastasis: Mechanisms and therapeutic implications","volume":"39","author":"Wei","year":"2020","journal-title":"Oncogene"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1089\/ars.2017.7176","article-title":"The roles of NRF2 in modulating cellular iron homeostasis","volume":"29","author":"Kerins","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Xiong, G., Feng, Y., Yi, X., Zhang, X., Li, X., Yang, L., Yi, Z., Sai, B., Yang, Z., and Zhang, Q. (2022). NRF2-directed PRPS1 upregulation to promote the progression and metastasis of melanoma. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.989263"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The emerging hallmarks of cancer metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/bs.ircmb.2017.12.002","article-title":"The Lymphatic Fluid","volume":"337","author":"Santambrogio","year":"2018","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e2411241122","DOI":"10.1073\/pnas.2411241122","article-title":"FAO-fueled OXPHOS and NRF2-mediated stress resilience in MICs drive lymph node metastasis","volume":"122","author":"Li","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.ccell.2016.05.005","article-title":"YAP\/TAZ at the Roots of Cancer","volume":"29","author":"Zanconato","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1093\/carcin\/bgq254","article-title":"YAP is a candidate oncogene for esophageal squamous cell carcinoma","volume":"32","author":"Muramatsu","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e57761","DOI":"10.7554\/eLife.57761","article-title":"Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway","volume":"9","author":"Chai","year":"2020","journal-title":"eLife"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e26597","DOI":"10.1097\/MD.0000000000026597","article-title":"Clinical significance of YAP1 and TAZ in esophageal squamous cell carcinoma","volume":"100","author":"Liu","year":"2021","journal-title":"Medicine"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1126\/science.aav0173","article-title":"Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation","volume":"363","author":"Lee","year":"2019","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3164\/jcbn.13-92","article-title":"Role of Nrf2 in the alteration of cholesterol and bile acid metabolism-related gene expression by dietary cholesterol in high fat-fed mice","volume":"54","author":"Kamisako","year":"2014","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Escoll, M., Lastra, D., Pajares, M., Robledinos-Anton, N., Rojo, A.I., Fernandez-Gines, R., Mendiola, M., Martinez-Marin, V., Esteban, I., and Lopez-Larrubia, P. (2020). Transcription factor NRF2 uses the Hippo pathway effector TAZ to induce tumorigenesis in glioblastomas. Redox Biol., 30.","DOI":"10.1016\/j.redox.2019.101425"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1074\/jbc.RA118.005963","article-title":"Hyperactivity of the transcription factor Nrf2 causes metabolic reprogramming in mouse esophagus","volume":"294","author":"Fu","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.freeradbiomed.2017.12.005","article-title":"Crosstalk between Nrf2 and YAP contributes to maintaining the antioxidant potential and chemoresistance in bladder cancer","volume":"115","author":"Ciamporcero","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/s41392-023-01589-z","article-title":"Recent advances in targeting the \u201cundruggable\u201d proteins: From drug discovery to clinical trials","volume":"8","author":"Xie","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Paiboonrungruang, C., Xiong, Z., Lamson, D., Li, Y., Bowman, B., Chembo, J., Huang, C., Li, J., Livingston, E.W., and Frank, J.E. (2023). Small molecule screen identifies pyrimethamine as an inhibitor of NRF2-driven esophageal hyperplasia. Redox Biol., 67.","DOI":"10.1016\/j.redox.2023.102901"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Chembo, J., Bowman, B.M., Lapak, K., Wilkerson, E., Paiboonrungruang, C., Cho, K., Medcalf, M.R., Patti, G.J., Dolle, R.E., and Chen, X. (2025). Pyrimethamine and a potent analogue WCDD115 inhibit NRF2 by suppressing DHFR and one-carbon metabolism. bioRxiv.","DOI":"10.1101\/2025.02.13.637433"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1248\/bpb.b22-00010","article-title":"Role of Nrf2 in Methotrexate-Induced Epithelial-Mesenchymal Transition in Alveolar A549 Cells","volume":"45","author":"Kawami","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1158\/1078-0432.CCR-24-1317","article-title":"Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis","volume":"30","author":"Lizardo","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Guo, L., Yang, Y., Ma, J., Xiao, M., Cao, R., Xi, Y., Li, T., Huang, T., and Yan, M. (2024). Triptolide induces hepatotoxicity by promoting ferroptosis through Nrf2 degradation. Cell Biol. Toxicol., 40.","DOI":"10.1007\/s10565-024-09930-0"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"9964","DOI":"10.1073\/pnas.1913633117","article-title":"Triptolide suppresses IDH1-mutated malignancy via Nrf2-driven glutathione metabolism","volume":"117","author":"Yu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1039\/D2MD00211F","article-title":"Exploring structural effects in a new class of NRF2 inhibitors","volume":"14","author":"Hou","year":"2023","journal-title":"RSC Med. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1158\/1535-7163.MCT-21-0210","article-title":"A Novel Nrf2 Pathway Inhibitor Sensitizes Keap1-Mutant Lung Cancer Cells to Chemotherapy","volume":"20","author":"Zhang","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Roy, N., Wyseure, T., Lo, I.-C., Metzger, J., Esissler, C.L., Bernard, S.M., Bok, I., Snead, A.N., Parker, A., and Green, J.C. (2024). Suppression of NRF2-dependent cancer growth by a covalent allosteric molecular glue. bioRxiv.","DOI":"10.1101\/2024.10.04.616592"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"113104","DOI":"10.1016\/j.celrep.2023.113104","article-title":"A NRF2 inhibitor selectively sensitizes KEAP1 mutant tumor cells to cisplatin and gefitinib by restoring NRF2-inhibitory function of KEAP1 mutants","volume":"42","author":"Aboulkassim","year":"2023","journal-title":"Cell Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1021\/acs.jmedchem.2c01909","article-title":"ARE-PROTACs Enable Co-degradation of an Nrf2-MafG Heterodimer","volume":"66","author":"Ji","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_137","unstructured":"Read, T.J., Steel, R., Damon, L., Yoo, R., Goliaei, A., Rimel, J., Hsu, J., Simpson, D., and Azofeifa, J. (2025, January 25\u201330). Discovery of a novel molecular glue degrader of Nrf2. Proceedings of the AACR 2025, Chicago, IL, USA."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"113686","DOI":"10.1016\/j.ejmech.2021.113686","article-title":"Discovery and characterization of novel peptide inhibitors of the NRF2\/MAFG\/DNA ternary complex for the treatment of cancer","volume":"224","author":"Simov","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Wiedemann, B., Kamps, D., Depta, L., Weisner, J., Cvetreznik, J., Tomassi, S., Gentz, S., Hoffmann, J.E., Muller, M.P., and Koch, O. (2022). Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0267651"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.1021\/acs.jmedchem.2c02037","article-title":"Stapled Peptides as Direct Inhibitors of Nrf2-sMAF Transcription Factors","volume":"66","author":"Modi","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"10240","DOI":"10.1523\/JNEUROSCI.1683-07.2007","article-title":"Enhancing expression of Nrf2-driven genes protects the blood brain barrier after brain injury","volume":"27","author":"Zhao","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/s41388-023-02636-3","article-title":"Repurposed pizotifen malate targeting NRF2 exhibits anti-tumor activity through inducing ferroptosis in esophageal squamous cell carcinoma","volume":"42","author":"He","year":"2023","journal-title":"Oncogene"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.cell.2022.04.014","article-title":"Systematic discovery of mutation-directed neo-protein-protein interactions in cancer","volume":"185","author":"Mo","year":"2022","journal-title":"Cell"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1021\/acs.accounts.5b00365","article-title":"Deoxynyboquinones as NQO1-Activated Cancer Therapeutics","volume":"48","author":"Parkinson","year":"2015","journal-title":"Acc. Chem. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1158\/0008-5472.CAN-09-3237","article-title":"The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3","volume":"70","author":"Guise","year":"2010","journal-title":"Cancer Res."},{"key":"ref_146","first-page":"3645","article-title":"A novel selective AKR1C3-activated prodrug AST-3424\/OBI-3424 exhibits broad anti-tumor activity","volume":"11","author":"Meng","year":"2021","journal-title":"Am. J. Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.1038\/s41388-022-02379-7","article-title":"AKR1C3 regulated by NRF2\/MAFG complex promotes proliferation via stabilizing PARP1 in hepatocellular carcinoma","volume":"41","author":"Pan","year":"2022","journal-title":"Oncogene"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"eabk1023","DOI":"10.1126\/sciadv.abk1023","article-title":"Activation of the NRF2 antioxidant program sensitizes tumors to G6PD inhibition","volume":"7","author":"Ding","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"e28083","DOI":"10.7554\/eLife.28083","article-title":"Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer","volume":"6","author":"Sayin","year":"2017","journal-title":"eLife"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"eabq5925","DOI":"10.1126\/sciadv.abq5925","article-title":"Discovery of DRP-104, a tumor-targeted metabolic inhibitor prodrug","volume":"8","author":"Rais","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jtho.2022.09.225","article-title":"Targeting NFE2L2\/KEAP1 Mutations in Advanced NSCLC With the TORC1\/2 Inhibitor TAK-228","volume":"18","author":"Paik","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3892\/ijo.2013.2229","article-title":"Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine","volume":"44","author":"Duong","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"113629","DOI":"10.1016\/j.celrep.2023.113629","article-title":"Metabolic reprogramming by histone deacetylase inhibition preferentially targets NRF2-activated tumors","volume":"43","author":"Karagiannis","year":"2024","journal-title":"Cell Rep."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Afjei, R., Sadeghipour, N., Kumar, S.U., Pandrala, M., Kumar, V., Malhotra, S.V., Massoud, T.F., and Paulmurugan, R. (2022). A New Nrf2 Inhibitor Enhances Chemotherapeutic Effects in Glioblastoma Cells Carrying p53 Mutations. Cancers, 14.","DOI":"10.3390\/cancers14246120"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Bae, E.S., Byun, W.S., Ock, C.W., Kim, W.K., Park, H.J., and Lee, S.K. (2023). Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells. Biomed. Pharmacother., 157.","DOI":"10.1016\/j.biopha.2022.114039"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.18632\/oncotarget.13825","article-title":"Discovery of a novel Nrf2 inhibitor that induces apoptosis of human acute myeloid leukemia cells","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Du, L., Zhu, X., Jiang, Z., Wang, W., Liu, P., Zhu, L., and Zhang, F. (2024). Resveratrol inhibits ferroptosis in the lung tissues of heat stroke-induced rats via the Nrf2 pathway. BMC Pharmacol. Toxicol., 25.","DOI":"10.1186\/s40360-024-00810-1"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/med.21364","article-title":"Mitoxantrone, More than Just Another Topoisomerase II Poison","volume":"36","author":"Evison","year":"2016","journal-title":"Med. Res. Rev."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"13943","DOI":"10.1073\/pnas.93.24.13943","article-title":"NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development","volume":"93","author":"Chan","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.1038\/onc.2017.153","article-title":"A clinical drug library screen identifies clobetasol propionate as an NRF2 inhibitor with potential therapeutic efficacy in KEAP1 mutant lung cancer","volume":"36","author":"Choi","year":"2017","journal-title":"Oncogene"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature10189","article-title":"Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis","volume":"475","author":"DeNicola","year":"2011","journal-title":"Nature"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ccell.2017.12.003","article-title":"Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase","volume":"33","author":"Gwinn","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_163","unstructured":"Islam, S., Jin, H., Liu, D., Lu, D., Zhang, Y., Chang, R., Austin, J., Beer, T., Tang, H., and Huang, L. (2025, January 25\u201330). Combinatorial use of VHL and KEAP1-based PROTACs reveals unexpected synergy and hook effect relief. Proceedings of the AACR 2025, Chicago, IL, USA."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"10268","DOI":"10.1021\/acs.jmedchem.5c00443","article-title":"Rational Design of Dual Degraders by Incorporating Molecular Glue Structural Features into PROTAC Degraders","volume":"68","author":"Zhang","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.omtn.2022.06.012","article-title":"DNA minicircles as novel STAT3 decoy oligodeoxynucleotides endowed with anticancer activity in triple-negative breast cancer","volume":"29","author":"Casas","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.freeradbiomed.2025.03.034","article-title":"The clinical-grade CBP\/p300 inhibitor CCS1477 represses the global NRF2-dependent cytoprotective transcription program and re-sensitizes cancer cells to chemotherapeutic drugs","volume":"233","author":"Wang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1021\/acs.bioconjchem.0c00082","article-title":"Recent Trends in In Situ Enzyme-Activatable Prodrugs for Targeted Cancer Therapy","volume":"31","author":"Sun","year":"2020","journal-title":"Bioconjug. Chem."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e00377-20","DOI":"10.1128\/MCB.00377-20","article-title":"Geldanamycin-Derived HSP90 Inhibitors Are Synthetic Lethal with NRF2","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/10985549.2024.2438817","article-title":"Anticancer Effect of C19-Position Substituted Geldanamycin Derivatives Targeting NRF2-NQO1-activated Esophageal Squamous Cell Carcinoma","volume":"45","author":"Oshikiri","year":"2024","journal-title":"Mol. Cell. Biol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"e00473-20","DOI":"10.1128\/MCB.00473-20","article-title":"NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer","volume":"41","author":"Baird","year":"2021","journal-title":"Mol. Cell. Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1158\/0008-5472.CAN-11-3135","article-title":"An NQO1 substrate with potent antitumor activity that selectively kills by PARP1-induced programmed necrosis","volume":"72","author":"Huang","year":"2012","journal-title":"Cancer Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1002\/iub.2680","article-title":"Novel NRF2-activated cancer treatments utilizing synthetic lethality","volume":"74","author":"Baird","year":"2022","journal-title":"IUBMB Life"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.cmet.2023.03.011","article-title":"NRF2 activation induces NADH-reductive stress, providing a metabolic vulnerability in lung cancer","volume":"35","author":"Ge","year":"2023","journal-title":"Cell Metab."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.trecan.2023.10.002","article-title":"Reductive stress in cancer: Coming out of the shadows","volume":"10","author":"Ge","year":"2024","journal-title":"Trends Cancer"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"eabo0404","DOI":"10.1126\/sciadv.abo0404","article-title":"G6PD-mediated increase in de novo NADP(+) biosynthesis promotes antioxidant defense and tumor metastasis","volume":"8","author":"Zhang","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1038\/nm.4407","article-title":"Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis","volume":"23","author":"Romero","year":"2017","journal-title":"Nat. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"eadm9859","DOI":"10.1126\/sciadv.adm9859","article-title":"Glutamine antagonist DRP-104 suppresses tumor growth and enhances response to checkpoint blockade in KEAP1 mutant lung cancer","volume":"10","author":"Pillai","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"7430","DOI":"10.1158\/0008-5472.CAN-14-1439","article-title":"Oncogenic KRAS confers chemoresistance by upregulating NRF2","volume":"74","author":"Tao","year":"2014","journal-title":"Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/ncb3341","article-title":"Glutathione biosynthesis is a metabolic vulnerability in PI(3)K\/Akt-driven breast cancer","volume":"18","author":"Lien","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1053\/j.gastro.2020.06.050","article-title":"TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines","volume":"159","author":"Jiang","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"5583","DOI":"10.1002\/ptr.8328","article-title":"Procyanidin B1 Promotes PSMC3-NRF2 Ubiquitination to Induce Ferroptosis in Glioblastoma","volume":"38","author":"Gao","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"2193","DOI":"10.1021\/acschembio.5b00448","article-title":"A Small Molecule Inhibits Deregulated NRF2 Transcriptional Activity in Cancer","volume":"10","author":"Bollong","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1021\/acschembio.6b00651","article-title":"Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors","volume":"11","author":"Singh","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/s41392-022-00994-0","article-title":"Artificial intelligence in cancer target identification and drug discovery","volume":"7","author":"You","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/d41573-024-00187-0","article-title":"The targeted protein degradation landscape","volume":"24","author":"Farley","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"9278","DOI":"10.1021\/acs.jmedchem.3c00449","article-title":"Molecular Glue Discovery: Current and Future Approaches","volume":"66","author":"Dewey","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1021\/acs.biochem.2c00245","article-title":"Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic","volume":"62","author":"Sasso","year":"2023","journal-title":"Biochemistry"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-pharmtox-022123-104147","article-title":"From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation","volume":"64","author":"Oleinikovas","year":"2024","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1021\/acs.jcim.2c01191","article-title":"Chemistry42: An AI-Driven Platform for Molecular Design and Optimization","volume":"63","author":"Ivanenkov","year":"2023","journal-title":"J. Chem. Inf. Model."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41587-024-02143-0","article-title":"A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models","volume":"43","author":"Ren","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"ref_191","unstructured":"Xiong, Z., Ladd, Z., Bui-Linh, C., Spitz, F., Wang, H., and Chen, X. (2025, January 10\u201312). AI-assisted Design of Novel NRF2Mut Inhibitors. Proceedings of the AACR Special Conference in Cancer Research: Artificial Intelligence and Machine Learning, Montreal, QC, Canada."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"100647","DOI":"10.1016\/j.mcpro.2023.100647","article-title":"Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC","volume":"22","author":"Wamsley","year":"2023","journal-title":"Mol. Cell. Proteom."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.redox.2018.07.026","article-title":"A distinct class of antioxidant response elements is consistently activated in tumors with NRF2 mutations","volume":"19","author":"Levings","year":"2018","journal-title":"Redox Biol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/s41568-023-00576-4","article-title":"Advances in PET imaging of cancer","volume":"23","author":"Schwenck","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1158\/1078-0432.CCR-18-3423","article-title":"Measurement of Tumor Antioxidant Capacity and Prediction of Chemotherapy Resistance in Preclinical Models of Ovarian Cancer by Positron Emission Tomography","volume":"25","author":"Greenwood","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1158\/0008-5472.CAN-18-2634","article-title":"Assessment of Tumor Redox Status through (S)-4-(3-[(18)F]fluoropropyl)-L-Glutamic Acid PET Imaging of System x(c) (-) Activity","volume":"79","author":"McCormick","year":"2019","journal-title":"Cancer Res."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/978-1-0716-3499-8_14","article-title":"Imaging the Tumor Antioxidant Response with [(18)F]FSPG PET","volume":"2729","author":"Timmermand","year":"2024","journal-title":"Methods Mol. Biol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.7150\/thno.63237","article-title":"Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x(C)(-) in tumors","volume":"12","author":"Greenwood","year":"2022","journal-title":"Theranostics"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.redox.2015.03.003","article-title":"Expression of xCT and activity of system xc(-) are regulated by NRF2 in human breast cancer cells in response to oxidative stress","volume":"5","author":"Habib","year":"2015","journal-title":"Redox Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"10484","DOI":"10.1038\/s41467-024-54852-4","article-title":"Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography","volume":"15","author":"Greenwood","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.1038\/s41467-024-48364-4","article-title":"PPIA dictates NRF2 stability to promote lung cancer progression","volume":"15","author":"Lu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Lister, A., Bourgeois, S., Imenez Silva, P.H., Rubio-Aliaga, I., Marbet, P., Walsh, J., Shelton, L.M., Keller, B., Verrey, F., and Devuyst, O. (2018). NRF2 regulates the glutamine transporter Slc38a3 (SNAT3) in kidney in response to metabolic acidosis. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-24000-2"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.2967\/jnumed.120.250977","article-title":"Kinetic Modeling of (18)F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism","volume":"62","author":"Viswanath","year":"2021","journal-title":"J. Nucl. Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1148\/radiol.2017162610","article-title":"In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of (18)F-(2S,4R)-4-Fluoroglutamine","volume":"287","author":"Dunphy","year":"2018","journal-title":"Radiology"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1158\/0008-5472.CAN-16-1945","article-title":"[(18)F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple-Negative Breast Cancer in Response to Glutaminase Inhibition","volume":"77","author":"Zhou","year":"2017","journal-title":"Cancer Res."},{"key":"ref_206","first-page":"3106","article-title":"SLC7A11\/xCT in cancer: Biological functions and therapeutic implications","volume":"10","author":"Lin","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3390\/tomography9020041","article-title":"Feasibility of [(18)F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer","volume":"9","author":"Bae","year":"2023","journal-title":"Tomography"},{"key":"ref_208","first-page":"37","article-title":"Esophageal cancer: Insights from mouse models","volume":"8","year":"2015","journal-title":"Cancer Growth Metastasis"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"104068","DOI":"10.1016\/j.critrevonc.2023.104068","article-title":"Preclinical tumor mouse models for studying esophageal cancer","volume":"189","author":"Mahmoudian","year":"2023","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1172\/JCI0215324","article-title":"A mouse model of human oral-esophageal cancer","volume":"110","author":"Opitz","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.ejca.2003.11.021","article-title":"Orthotopic models of cancer for preclinical drug evaluation: Advantages and disadvantages","volume":"40","author":"Bibby","year":"2004","journal-title":"Eur. J. Cancer"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1023\/A:1006326203858","article-title":"Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: A bridge to the clinic","volume":"17","author":"Hoffman","year":"1999","journal-title":"Investig. New Drugs"},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Ip, J.C., Ko, J.M., Yu, V.Z., Chan, K.W., Lam, A.K., Law, S., Tong, D.K., and Lung, M.L. (2015). A versatile orthotopic nude mouse model for study of esophageal squamous cell carcinoma. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/910715"},{"key":"ref_214","doi-asserted-by":"crossref","unstructured":"Kuroda, S., Kubota, T., Aoyama, K., Kikuchi, S., Tazawa, H., Nishizaki, M., Kagawa, S., and Fujiwara, T. (2014). Establishment of a Non-Invasive Semi-Quantitative Bioluminescent Imaging Method for Monitoring of an Orthotopic Esophageal Cancer Mouse Model. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114562"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/labinvest.2014.77","article-title":"Establishment and characterization of esophageal squamous cell carcinoma patient-derived xenograft mouse models for preclinical drug discovery","volume":"94","author":"Zhang","year":"2014","journal-title":"Lab. Investig."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41571-022-00721-2","article-title":"Humanized mouse models for immuno-oncology research","volume":"20","author":"Chuprin","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1158\/0008-5472.CAN-22-1903","article-title":"NFE2L2 Mutations Enhance Radioresistance in Head and Neck Cancer by Modulating Intratumoral Myeloid Cells","volume":"83","author":"Guan","year":"2023","journal-title":"Cancer Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1002\/cac2.12066","article-title":"A new mouse esophageal cancer cell line (mEC25)-derived pre-clinical syngeneic tumor model for immunotherapy","volume":"40","author":"Huang","year":"2020","journal-title":"Cancer Commun."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"106012","DOI":"10.1016\/j.oraloncology.2022.106012","article-title":"The mouse oral carcinoma (MOC) model: A 10-year retrospective on model development and head and neck cancer investigations","volume":"132","author":"Kono","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/cgt.2011.56","article-title":"Neoadjuvant in situ gene-mediated cytotoxic immunotherapy improves postoperative outcomes in novel syngeneic esophageal carcinoma models","volume":"18","author":"Predina","year":"2011","journal-title":"Cancer Gene Ther."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/(SICI)1097-0215(19990730)82:3<377::AID-IJC11>3.0.CO;2-9","article-title":"Decreased expression of CD80 is a marker for increased tumorigenicity in a new murine model of oral squamous-cell carcinoma","volume":"82","author":"Thomas","year":"1999","journal-title":"Int. J. Cancer"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature24297","article-title":"Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition","volume":"551","author":"Hangauer","year":"2017","journal-title":"Nature"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41586-021-03796-6","article-title":"Cycling cancer persister cells arise from lineages with distinct programs","volume":"596","author":"Oren","year":"2021","journal-title":"Nature"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1158\/0008-5472.CAN-22-2605","article-title":"Characterizing Evolutionary Dynamics Reveals Strategies to Exhaust the Spectrum of Subclonal Resistance in EGFR-Mutant Lung Cancer","volume":"83","author":"Muller","year":"2023","journal-title":"Cancer Res."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"6587","DOI":"10.1038\/s41467-024-50998-3","article-title":"Targeting fatty acid oxidation enhances response to HER2-targeted therapy","volume":"15","author":"Nandi","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s41568-024-00737-z","article-title":"Cancer drug-tolerant persister cells: From biological questions to clinical opportunities","volume":"24","author":"Russo","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Tan, Y., Huang, C., and Wei, X. (2023). Redox signaling in drug-tolerant persister cells as an emerging therapeutic target. EBioMedicine, 89.","DOI":"10.1016\/j.ebiom.2023.104483"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1038\/s41586-024-07690-9","article-title":"Cellular adaptation to cancer therapy along a resistance continuum","volume":"631","author":"Franca","year":"2024","journal-title":"Nature"},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Kerins, M.J., and Ooi, A. (2018). A catalogue of somatic NRF2 gain-of-function mutations in cancer. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-31281-0"},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.tcb.2019.08.009","article-title":"The Rise of Physiologic Media","volume":"29","author":"Cantor","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_231","first-page":"4924","article-title":"Use of lymph in cell culture to model hormonal and nutritional constraints on tumor growth in vivo","volume":"47","author":"Rubin","year":"1987","journal-title":"Cancer Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s10456-018-9629-2","article-title":"Fluorescent reporter transgenic mice for in vivo live imaging of angiogenesis and lymphangiogenesis","volume":"21","author":"Doh","year":"2018","journal-title":"Angiogenesis"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"eabc1944","DOI":"10.1126\/science.abc1944","article-title":"Single-cell lineages reveal the rates, routes, and drivers of metastasis in cancer xenografts","volume":"371","author":"Quinn","year":"2021","journal-title":"Science"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1146\/annurev-med-051419-114417","article-title":"Lymphatic Vasculature: An Emerging Therapeutic Target and Drug Delivery Route","volume":"72","author":"Xu","year":"2021","journal-title":"Annu. Rev. Med."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Kodama, T., Matsuki, D., Tada, A., Takeda, K., and Mori, S. (2016). New concept for the prevention and treatment of metastatic lymph nodes using chemotherapy administered via the lymphatic network. Sci. Rep., 6.","DOI":"10.1038\/srep32506"},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Oladipo, A.O., Oluwafemi, O.S., Songca, S.P., Sukhbaatar, A., Mori, S., Okajima, J., Komiya, A., Maruyama, S., and Kodama, T. (2017). A novel treatment for metastatic lymph nodes using lymphatic delivery and photothermal therapy. Sci. Rep., 7.","DOI":"10.1038\/srep45459"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nrd4608","article-title":"From sewer to saviour\u2014Targeting the lymphatic system to promote drug exposure and activity","volume":"14","author":"Trevaskis","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"R474","DOI":"10.1186\/bcr819","article-title":"Drug concentrations in axillary lymph nodes after lymphatic chemotherapy on patients with breast cancer","volume":"6","author":"Chen","year":"2004","journal-title":"Breast Cancer Res."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/ng1248","article-title":"Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation","volume":"35","author":"Wakabayashi","year":"2003","journal-title":"Nat. Genet."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1853\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:44:52Z","timestamp":1760031892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/11\/1853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,31]]},"references-count":239,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["cancers17111853"],"URL":"https:\/\/doi.org\/10.3390\/cancers17111853","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,31]]}}}