{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:07:03Z","timestamp":1785762423223,"version":"3.56.0"},"reference-count":222,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Squamous cell carcinomas (SCCs) arise from both stratified squamous and non-squamous epithelium of diverse anatomical sites and collectively represent one of the most frequent solid tumors, accounting for more than one million cancer deaths annually. Despite this prevalence, SCC patients have not fully benefited from recent advances in molecularly targeted therapy or immunotherapy. Rather, decades old platinum-based or radiation regimens retaining limited specificity to the unique characteristics of SCC remain first-line treatment options. Historically, a lack of a consolidated perspective on genetic aberrations driving oncogenic transformation and other such factors essential for SCC pathogenesis and intrinsic confounding cellular heterogeneity in SCC have contributed to a critical dearth in effective and specific therapies. However, emerging evidence characterizing the distinct genomic, epigenetic, and metabolic landscapes of SCC may be elucidating unifying features in a seemingly heterogeneous disease. In this review, by describing distinct metabolic alterations and genetic drivers of SCC revealed by recent studies, we aim to establish a conceptual framework for a previously unappreciated network of oncogenic signaling, redox perturbation, and metabolic reprogramming that may reveal targetable vulnerabilities at their intersection.<\/jats:p>","DOI":"10.3390\/cells10030606","type":"journal-article","created":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T12:08:01Z","timestamp":1615291681000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Oxidative Stress and the Intersection of Oncogenic Signaling and Metabolism in Squamous Cell Carcinomas"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7094-3766","authenticated-orcid":false,"given":"Joshua H.","family":"Choe","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6554-7889","authenticated-orcid":false,"given":"Simbarashe","family":"Mazambani","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3950-7557","authenticated-orcid":false,"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-1480","authenticated-orcid":false,"given":"Jung-whan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX 75080, USA"},{"name":"Research and Development, VeraVerse Inc., 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10555-010-9214-7","article-title":"Natural history of bronchial preinvasive lesions","volume":"29","author":"Ishizumi","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41568-018-0024-5","article-title":"Deciphering the cells of origin of squamous cell carcinomas","volume":"18","author":"Blanpain","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1038\/ncomms4261","article-title":"Transdifferentiation of lung adenocarcinoma in mice with Lkb1 deficiency to squamous cell carcinoma","volume":"5","author":"Han","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1097\/JTO.0000000000000571","article-title":"Histologic Transformation from Adenocarcinoma to Squamous Cell Carcinoma as a Mechanism of Resistance to EGFR Inhibition","volume":"10","author":"Levin","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_5","first-page":"275","article-title":"Squamous Cell Carcinoma - Similarities and Differences among Anatomical Sites","volume":"1","author":"Yan","year":"2011","journal-title":"Am. J. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7431","DOI":"10.1073\/pnas.1012720108","article-title":"Identifying the cellular origin of squamous skin tumors","volume":"108","author":"Lapouge","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7425","DOI":"10.1073\/pnas.1012670108","article-title":"Defining the origins of Ras\/p53-mediated squamous cell carcinoma","volume":"108","author":"White","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1101\/gad.338228.120","article-title":"Cells of origin of lung cancers: Lessons from mouse studies","volume":"34","author":"Ferone","year":"2020","journal-title":"Genes Dev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cell.2014.06.049","article-title":"Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin","volume":"158","author":"Hoadley","year":"2014","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1126\/science.1208130","article-title":"The Mutational Landscape of Head and Neck Squamous Cell Carcinoma","volume":"333","author":"Stransky","year":"2011","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Network (2015). Comprehensive genomic characterization of head and neck squamous cell carcinomas. Nature, 517, 576\u2013582.","DOI":"10.1038\/nature14129"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2012). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 489, 519\u2013525.","DOI":"10.1038\/nature11404"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of urothelial bladder carcinoma. Nature, 507, 315\u2013322.","DOI":"10.1038\/nature12965"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2017). Integrated genomic and molecular characterization of cervical cancer. Nature, 543, 378\u2013384.","DOI":"10.1038\/nature21386"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network (2017). Integrated genomic characterization of oesophageal carcinoma. Nature, 541, 169\u2013175.","DOI":"10.1038\/nature20805"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1056\/NEJMoa053422","article-title":"Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck","volume":"354","author":"Bonner","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.ccell.2015.03.010","article-title":"AXL mediates resistance to PI3Kalpha inhibition by activating the EGFR\/PKC\/mTOR axis in head and neck and esophageal squamous cell carcinomas","volume":"27","author":"Elkabets","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1056\/NEJMoa0802656","article-title":"Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer","volume":"359","author":"Vermorken","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.stem.2017.10.001","article-title":"TGF-beta-Induced Quiescence Mediates Chemoresistance of Tumor-Propagating Cells in Squamous Cell Carcinoma","volume":"21","author":"Brown","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa1504627","article-title":"Nivolumab versus Docetaxel in Advanced Squamous-Cell Non\u2013Small-Cell Lung Cancer","volume":"373","author":"Brahmer","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3109\/10715761003667554","article-title":"Reactive oxygen species in cancer","volume":"44","author":"Liou","year":"2010","journal-title":"Free Radic. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2017.01.004","article-title":"Reactive oxygen species and cancer paradox: To promote or to suppress?","volume":"104","author":"Galadari","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1477-3163-5-14","article-title":"Reactive oxygen species: Role in the development of cancer and various chronic conditions","volume":"5","author":"Waris","year":"2006","journal-title":"J. Carcinog."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ccr.2006.12.013","article-title":"p38alpha MAP kinase as a sensor of reactive oxygen species in tumorigenesis","volume":"11","author":"Dolado","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ccr.2007.08.004","article-title":"HIF-dependent antitumorigenic effect of antioxidants in vivo","volume":"12","author":"Gao","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1177271918755391","DOI":"10.1177\/1177271918755391","article-title":"Reactive Oxygen Species: A Key Constituent in Cancer Survival","volume":"13","author":"Kumari","year":"2018","journal-title":"Biomark. Insights"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s12276-020-0384-2","article-title":"ROS in cancer therapy: The bright side of the moon","volume":"52","author":"Perillo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/s41392-020-00326-0","article-title":"NADPH homeostasis in cancer: Functions, mechanisms and therapeutic implications","volume":"5","author":"Ju","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cell.2020.05.039","article-title":"Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma","volume":"182","author":"Ji","year":"2020","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/sj.bjc.6600688","article-title":"Human papillomavirus types in invasive cervical cancer worldwide: A meta-analysis","volume":"88","author":"Clifford","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1093\/aje\/kwm051","article-title":"A Prospective Study of Tobacco, Alcohol, and the Risk of Esophageal and Gastric Cancer Subtypes","volume":"165","author":"Freedman","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/366023a0","article-title":"Skin cancer and UV radiation","volume":"366","author":"Madronich","year":"1993","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.ccell.2016.04.004","article-title":"Squamous Cell Cancers: A Unified Perspective on Biology and Genetics","volume":"29","author":"Dotto","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1016\/j.jid.2017.03.027","article-title":"Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma","volume":"137","author":"Dusingize","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","first-page":"85","article-title":"Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: Adenocarcinoma versus squamous cell carcinoma","volume":"4","author":"Vaughan","year":"1995","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0169-5002(00)00181-1","article-title":"Effect of cigarette smoking on major histological types of lung cancer: A meta-analysis","volume":"31","author":"Khuder","year":"2001","journal-title":"Lung Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1001\/jamainternmed.2015.2398","article-title":"Deaths Due to Cigarette Smoking for 12 Smoking-Related Cancers in the United StatesCigarette Smoking Deaths for Smoking-Related CancersLetters","volume":"175","author":"Siegel","year":"2015","journal-title":"JAMA Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1126\/science.aag0299","article-title":"Mutational signatures associated with tobacco smoking in human cancer","volume":"354","author":"Alexandrov","year":"2016","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/jnci\/91.14.1194","article-title":"Tobacco smoke carcinogens and lung cancer","volume":"91","author":"Hecht","year":"1999","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/nrc1190","article-title":"Tobacco carcinogens, their biomarkers and tobacco-induced cancer","volume":"3","author":"Hecht","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7435","DOI":"10.1038\/sj.onc.1205803","article-title":"Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers","volume":"21","author":"Pfeifer","year":"2002","journal-title":"Oncogene"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/carcin\/18.9.1763","article-title":"Cigarette smoking induces an increase in oxidative DNA damage, 8-hydroxydeoxyguanosine, in a central site of the human lung","volume":"18","author":"Asami","year":"1997","journal-title":"Carcinogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/nrd4002","article-title":"Modulation of oxidative stress as an anticancer strategy","volume":"12","author":"Gorrini","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1126\/science.6301009","article-title":"The radicals in cigarette tar: Their nature and suggested physiological implications","volume":"220","author":"Pryor","year":"1983","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"ROS Function in Redox Signaling and Oxidative Stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.oraloncology.2006.02.013","article-title":"Enhanced lipid peroxidation and nitric oxide products with deranged antioxidant status in patients with head and neck squamous cell carcinoma","volume":"43","author":"Rasheed","year":"2007","journal-title":"Oral Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Shareck, M., Rousseau, M.-C., Koushik, A., Siemiatycki, J., and Parent, M.-E. (2017). Inverse Association between Dietary Intake of Selected Carotenoids and Vitamin C and Risk of Lung Cancer. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00023"},{"key":"ref_48","first-page":"813","article-title":"Alcohol Consumption and Lung Cancer","volume":"10","author":"Bandera","year":"2001","journal-title":"Rev. Epidemiol. Evid."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1470-2045(06)70577-0","article-title":"Alcohol and cancer","volume":"7","author":"Boffetta","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1080\/01635581.2016.1158296","article-title":"Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies","volume":"68","author":"Siiskonen","year":"2016","journal-title":"Nutr. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15290","DOI":"10.1038\/ncomms15290","article-title":"Genomic analysis of oesophageal squamous-cell carcinoma identifies alcohol drinking-related mutation signature and genomic alterations","volume":"8","author":"Chang","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/em.21824","article-title":"Acetaldehyde and the genome: Beyond nuclear DNA adducts and carcinogenesis","volume":"55","author":"Brooks","year":"2014","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1159\/000090167","article-title":"Alcohol-related diseases of the esophagus and stomach","volume":"23","author":"Franke","year":"2005","journal-title":"Dig. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.alcohol.2005.03.012","article-title":"Effects of alcohol on folate metabolism: Implications for carcinogenesis","volume":"35","author":"Mason","year":"2005","journal-title":"Alcohol"},{"key":"ref_55","first-page":"277","article-title":"Alcohol, oxidative stress, and free radical damage","volume":"27","author":"Wu","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/bjc.2014.579","article-title":"Alcohol consumption and site-specific cancer risk: A comprehensive dose\u2013response meta-analysis","volume":"112","author":"Bagnardi","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_57","first-page":"1017","article-title":"Cervical cancer: Epidemiology, prevention and the role of human papillomavirus infection","volume":"164","author":"Franco","year":"2001","journal-title":"Can. Med. Assoc. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"918","DOI":"10.15585\/mmwr.mm6733a2","article-title":"Trends in Human Papillomavirus-Associated Cancers - United States, 1999-2015","volume":"67","author":"Henley","year":"2018","journal-title":"MMWR. Morb. Mortal. Wkly. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jaad.2014.01.857","article-title":"Role of human papillomavirus in cutaneous squamous cell carcinoma: A meta-analysis","volume":"70","author":"Wang","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1089\/jwh.2011.3385","article-title":"Cervical cancer trends in the United States: A 35-year population-based analysis","volume":"21","author":"Adegoke","year":"2012","journal-title":"J. Womens Health"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.3174\/ajnr.A5792","article-title":"Correlation between Human Papillomavirus Status and Quantitative MR Imaging Parameters including Diffusion-Weighted Imaging and Texture Features in Oropharyngeal Carcinoma","volume":"39","author":"Ravanelli","year":"2018","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Cho, S.Y., Kim, S., Son, M.-J., Kim, G., Singh, P., Kim, H.N., Choi, H.-G., Yoo, H.J., Ko, Y.B., and Lee, B.S. (2019). Dual oxidase 1 and NADPH oxidase 2 exert favorable effects in cervical cancer patients by activating immune response. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6202-3"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1093\/carcin\/bgv126","article-title":"HPV16 E6 and E7 proteins induce a chronic oxidative stress response via NOX2 that causes genomic instability and increased susceptibility to DNA damage in head and neck cancer cells","volume":"36","author":"Marullo","year":"2015","journal-title":"Carcinogenesis"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6751","DOI":"10.1128\/JVI.03355-13","article-title":"Human papillomavirus type 16 E6* induces oxidative stress and DNA damage","volume":"88","author":"Williams","year":"2014","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S1011-1344(01)00198-1","article-title":"The epidemiology of UV induced skin cancer","volume":"63","author":"Armstrong","year":"2001","journal-title":"J. Photochem. Photobiol. B"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1586\/17469872.2.4.451","article-title":"Mechanism of UV-related carcinogenesis and its contribution to nevi\/melanoma","volume":"2","author":"Anna","year":"2007","journal-title":"Expert Rev. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.semcancer.2003.09.017","article-title":"UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression","volume":"14","author":"Bachelor","year":"2004","journal-title":"Semin. Cancer Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.dnarep.2016.05.024","article-title":"Protein oxidation, UVA and human DNA repair","volume":"44","author":"Karran","year":"2016","journal-title":"DNA Repair"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1158\/1541-7786.MCR-16-0053","article-title":"Oxidative Stress-Induced Protein Damage Inhibits DNA Repair and Determines Mutation Risk and Therapeutic Efficacy","volume":"14","author":"McAdam","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1111\/j.1365-4632.2010.04474.x","article-title":"Ultraviolet radiation and skin cancer","volume":"49","author":"Narayanan","year":"2010","journal-title":"Int. J. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1046\/j.0022-202x.2001.01503.x","article-title":"Ultraviolet a radiation suppresses an established immune response: Implications for sunscreen design","volume":"117","author":"Nghiem","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/nrc.2017.68","article-title":"Metaplasia: Tissue injury adaptation and a precursor to the dysplasia-cancer sequence","volume":"17","author":"Giroux","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"eaaw0726","DOI":"10.1126\/science.aaw0726","article-title":"RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues","volume":"364","author":"Yizhak","year":"2019","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.ccell.2015.04.001","article-title":"LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response","volume":"27","author":"Li","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.cmet.2011.07.014","article-title":"Metabolic flux and the regulation of mammalian cell growth","volume":"14","author":"Locasale","year":"2011","journal-title":"Cell Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15503","DOI":"10.1038\/ncomms15503","article-title":"The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition","volume":"8","author":"Goodwin","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1097\/JTO.0b013e31815e6d6b","article-title":"Primary tumor standardized uptake value (SUVmax) measured on fluorodeoxyglucose positron emission tomography (FDG-PET) is of prognostic value for survival in non-small cell lung cancer (NSCLC): A systematic review and meta-analysis (MA) by the European Lung Cancer Working Party for the IASLC Lung Cancer Staging Project","volume":"3","author":"Berghmans","year":"2008","journal-title":"J. Thorac. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.lungcan.2006.08.018","article-title":"Biological correlates of FDG uptake in non-small cell lung cancer","volume":"55","author":"Aliredjo","year":"2007","journal-title":"Lung Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0169-5002(00)00250-6","article-title":"Correlation of FDG-PET imaging with Glut-1 and Glut-3 expression in early-stage non-small cell lung cancer","volume":"33","author":"Marom","year":"2001","journal-title":"Lung Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.lungcan.2011.11.006","article-title":"Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: Spatial distribution and prognostic value of GLUT1 and MCT4","volume":"76","author":"Meijer","year":"2012","journal-title":"Lung Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1016\/j.celrep.2019.07.027","article-title":"p63 and SOX2 Dictate Glucose Reliance and Metabolic Vulnerabilities in Squamous Cell Carcinomas","volume":"28","author":"Hsieh","year":"2019","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"De Schutter, H., Landuyt, W., Verbeken, E., Goethals, L., Hermans, R., and Nuyts, S. (2005). The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +\/- chemotherapy. BMC Cancer, 5.","DOI":"10.1186\/1471-2407-5-42"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"13301","DOI":"10.1038\/s41598-019-49928-x","article-title":"Differential effect of GLUT1 overexpression on survival and tumor immune microenvironment of human papilloma virus type 16-positive and -negative cervical cancer","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.oraloncology.2006.10.009","article-title":"Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity","volume":"43","author":"Kunkel","year":"2007","journal-title":"Oral Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature13236","article-title":"Quantitative flux analysis reveals folate-dependent NADPH production","volume":"510","author":"Fan","year":"2014","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e318","DOI":"10.1038\/emm.2017.15","article-title":"Inhibition of glutathione metabolism attenuates esophageal cancer progression","volume":"49","author":"Peng","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Sobhakumari, A., Love-Homan, L., Fletcher, E.V., Martin, S.M., Parsons, A.D., Spitz, D.R., Knudson, C.M., and Simons, A.L. (2012). Susceptibility of human head and neck cancer cells to combined inhibition of glutathione and thioredoxin metabolism. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048175"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41419-018-0635-5","article-title":"A new inhibitor of glucose-6-phosphate dehydrogenase blocks pentose phosphate pathway and suppresses malignant proliferation and metastasis in vivo","volume":"9","author":"Mele","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/s41416-019-0464-z","article-title":"Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes","volume":"121","author":"Sellers","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1101\/gad.14.1.34","article-title":"Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha","volume":"14","author":"Ravi","year":"2000","journal-title":"Genes Dev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"8211","DOI":"10.1073\/pnas.1435900100","article-title":"Human papillomavirus E6 and Myc proteins associate in vivo and bind to and cooperatively activate the telomerase reverse transcriptase promoter","volume":"100","author":"Veldman","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1073\/pnas.96.4.1291","article-title":"Modulation of type M2 pyruvate kinase activity by the human papillomavirus type 16 E7 oncoprotein","volume":"96","author":"Zwerschke","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/onc.2016.290","article-title":"LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism","volume":"36","author":"Zeng","year":"2017","journal-title":"Oncogene"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41416-018-0364-7","article-title":"HPV, tumour metabolism and novel target identification in head and neck squamous cell carcinoma","volume":"120","author":"Fleming","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"51530","DOI":"10.18632\/oncotarget.17887","article-title":"HPV-associated differential regulation of tumor metabolism in oropharyngeal head and neck cancer","volume":"8","author":"Jung","year":"2017","journal-title":"Oncotarget"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Prusinkiewicz, M.A., Gameiro, S.F., Ghasemi, F., Dodge, M.J., Zeng, P.Y.F., Maekebay, H., Barrett, J.W., Nichols, A.C., and Mymryk, J.S. (2020). Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers. Cancers, 12.","DOI":"10.3390\/cancers12010253"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41467-018-07857-9","article-title":"Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin","volume":"10","author":"Flores","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1158\/0008-5472.CAN-14-3745","article-title":"Amino Acid transporters in cancer and their relevance to \"glutamine addiction\": Novel targets for the design of a new class of anticancer drugs","volume":"75","author":"Bhutia","year":"2015","journal-title":"Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.ccr.2013.08.020","article-title":"Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target","volume":"24","author":"Timmerman","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/s41467-019-09179-w","article-title":"Targeting glutamine-addiction and overcoming CDK4\/6 inhibitor resistance in human esophageal squamous cell carcinoma","volume":"10","author":"Qie","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/s41416-019-0637-9","article-title":"ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma","volume":"122","author":"Zhang","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1002\/cam4.2965","article-title":"ASCT2 overexpression is associated with poor survival of OSCC patients and ASCT2 knockdown inhibited growth of glutamine-addicted OSCC cells","volume":"9","author":"Luo","year":"2020","journal-title":"Cancer Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.ccell.2018.04.002","article-title":"The GSK3 Signaling Axis Regulates Adaptive Glutamine Metabolism in Lung Squamous Cell Carcinoma","volume":"33","author":"Momcilovic","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Domingo-Vidal, M., Whitaker-Menezes, D., Martos-Rus, C., Tassone, P., Snyder, C.M., Tuluc, M., Philp, N., Curry, J., and Martinez-Outschoorn, U. (2019). Cigarette Smoke Induces Metabolic Reprogramming of the Tumor Stroma in Head and Neck Squamous Cell Carcinoma. Mol. Cancer Res.","DOI":"10.1158\/1541-7786.MCR-18-1191"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1158\/0008-5472.CAN-17-1076","article-title":"Cancer-Associated Fibroblasts Drive Glycolysis in a Targetable Signaling Loop Implicated in Head and Neck Squamous Cell Carcinoma Progression","volume":"78","author":"Kumar","year":"2018","journal-title":"Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5130","DOI":"10.1158\/0008-5472.CAN-12-1949","article-title":"Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay","volume":"72","author":"Fiaschi","year":"2012","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1158\/0008-5472.CAN-12-2796","article-title":"Acidity generated by the tumor microenvironment drives local invasion","volume":"73","author":"Estrella","year":"2013","journal-title":"Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1158\/0008-5472.CAN-18-1604","article-title":"Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes","volume":"79","author":"Rohani","year":"2019","journal-title":"Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13046-016-0481-1","article-title":"Blockage of glycolysis by targeting PFKFB3 suppresses tumor growth and metastasis in head and neck squamous cell carcinoma","volume":"36","author":"Li","year":"2017","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"9557","DOI":"10.18632\/oncotarget.13771","article-title":"EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect","volume":"8","author":"Xu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.cell.2017.09.019","article-title":"Lactate Metabolism in Human Lung Tumors","volume":"171","author":"Faubert","year":"2017","journal-title":"Cell"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Zhu, J., Wu, Y.N., Zhang, W., Zhang, X.M., Ding, X., Li, H.Q., Geng, M., Xie, Z.Q., and Wu, H.M. (2014). Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087904"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/j.1600-0560.2012.01912.x","article-title":"CD147 expression in advanced cutaneous squamous cell carcinoma","volume":"39","author":"Sweeny","year":"2012","journal-title":"J. Cutan. Pathol."},{"key":"ref_114","first-page":"3930","article-title":"Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1111\/j.1349-7006.2011.01908.x","article-title":"Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells","volume":"102","author":"Izumi","year":"2011","journal-title":"Cancer Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.1038\/onc.2013.454","article-title":"Glucose deprivation increases monocarboxylate transporter 1 (MCT1) expression and MCT1-dependent tumor cell migration","volume":"33","author":"Porporato","year":"2014","journal-title":"Oncogene"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1158\/0008-5472.CAN-17-0764","article-title":"Monocarboxylate Transporter MCT1 Promotes Tumor Metastasis Independently of Its Activity as a Lactate Transporter","volume":"77","author":"Payen","year":"2017","journal-title":"Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1126\/science.aab4082","article-title":"Somatic mutation in cancer and normal cells","volume":"349","author":"Martincorena","year":"2015","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1126\/science.aau3879","article-title":"Somatic mutant clones colonize the human esophagus with age","volume":"362","author":"Martincorena","year":"2018","journal-title":"Science"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.celrep.2019.12.071","article-title":"Chromosome 3q26 Gain Is an Early Event Driving Coordinated Overexpression of the PRKCI, SOX2, and ECT2 Oncogenes in Lung Squamous Cell Carcinoma","volume":"30","author":"Liu","year":"2020","journal-title":"Cell Rep."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ccell.2018.11.009","article-title":"The Roles of Initiating Truncal Mutations in Human Cancers: The Order of Mutations and Tumor Cell Type Matters","volume":"35","author":"Levine","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"8258","DOI":"10.1038\/ncomms9258","article-title":"Targeted sequencing reveals clonal genetic changes in the progression of early lung neoplasms and paired circulating DNA","volume":"6","author":"Izumchenko","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrc.2016.145","article-title":"Notch as a tumour suppressor","volume":"17","author":"Nowell","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nature22379","article-title":"Nutrient acquisition strategies of mammalian cells","volume":"546","author":"Palm","year":"2017","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1126\/science.1193494","article-title":"The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes","volume":"330","author":"Levine","year":"2010","journal-title":"Science"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1101\/gad.190678.112","article-title":"Mutant p53: One name, many proteins","volume":"26","author":"Prives","year":"2012","journal-title":"Genes Dev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"a001107","DOI":"10.1101\/cshperspect.a001107","article-title":"Mutant p53 gain-of-function in cancer","volume":"2","author":"Oren","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molmet.2019.10.002","article-title":"Metabolic functions of the tumor suppressor p53: Implications in normal physiology, metabolic disorders, and cancer","volume":"33","author":"Lacroix","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumour suppression","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1038\/ncomms3935","article-title":"Tumour-associated mutant p53 drives the Warburg effect","volume":"4","author":"Zhang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s40170-018-0191-6","article-title":"p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant","volume":"6","author":"Humpton","year":"2018","journal-title":"Cancer Metab."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"20508","DOI":"10.18632\/oncotarget.24974","article-title":"Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells","volume":"9","author":"Lisek","year":"2018","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1038\/bjc.2014.165","article-title":"Wild-type and mutant p53 differentially regulate NADPH oxidase 4 in TGF-\u03b2-mediated migration of human lung and breast epithelial cells","volume":"110","author":"Boudreau","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.molcel.2014.04.024","article-title":"Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation","volume":"54","author":"Zhou","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/s41388-017-0032-z","article-title":"Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cells by targeting the transcription factors FOXO3a and FOXM1","volume":"37","author":"Tanaka","year":"2018","journal-title":"Oncogene"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1158\/1078-0432.CCR-13-2407","article-title":"FOXM1 promotes the warburg effect and pancreatic cancer progression via transactivation of LDHA expression","volume":"20","author":"Cui","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Gemenetzidis, E., Bose, A., Riaz, A.M., Chaplin, T., Young, B.D., Ali, M., Sugden, D., Thurlow, J.K., Cheong, S.C., and Teo, S.H. (2009). FOXM1 upregulation is an early event in human squamous cell carcinoma and it is enhanced by nicotine during malignant transformation. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004849"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1038\/emboj.2009.239","article-title":"FoxM1, a critical regulator of oxidative stress during oncogenesis","volume":"28","author":"Park","year":"2009","journal-title":"EMBO J."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"47985","DOI":"10.18632\/oncotarget.10103","article-title":"FOXM1 promotes reprogramming of glucose metabolism in epithelial ovarian cancer cells via activation of GLUT1 and HK2 transcription","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.stem.2011.09.001","article-title":"Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice","volume":"9","author":"Arnold","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1146\/annurev-pathol-121808-102117","article-title":"p63 in epithelial survival, germ cell surveillance, and neoplasia","volume":"5","author":"Crum","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.celrep.2018.03.063","article-title":"Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas","volume":"23","author":"Campbell","year":"2018","journal-title":"Cell Rep."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ccell.2016.09.001","article-title":"SOX2 Is the Determining Oncogenic Switch in Promoting Lung Squamous Cell Carcinoma from Different Cells of Origin","volume":"30","author":"Ferone","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S1097-2765(00)80275-0","article-title":"p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities","volume":"2","author":"Yang","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"5462","DOI":"10.1073\/pnas.97.10.5462","article-title":"AIS is an oncogene amplified in squamous cell carcinoma","volume":"97","author":"Hibi","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.stem.2010.12.009","article-title":"DeltaNp63alpha is an oncogene that targets chromatin remodeler Lsh to drive skin stem cell proliferation and tumorigenesis","volume":"8","author":"Keyes","year":"2011","journal-title":"Cell Stem Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S1535-6108(02)00057-0","article-title":"DeltaNp63 induces beta-catenin nuclear accumulation and signaling","volume":"1","author":"Patturajan","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"936","DOI":"10.4161\/cc.5.9.2716","article-title":"p63 and p73: Life and death in squamous cell carcinoma","volume":"5","author":"Rocco","year":"2006","journal-title":"Cell Cycle"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1172\/JCI71545","article-title":"SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas","volume":"124","author":"Watanabe","year":"2014","journal-title":"J. Clin. Invest."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"11577","DOI":"10.1073\/pnas.1508871112","article-title":"p63 supports aerobic respiration through hexokinase II","volume":"112","author":"Viticchie","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"2926","DOI":"10.1016\/j.celrep.2017.11.030","article-title":"DeltaNp63 Inhibits Oxidative Stress-Induced Cell Death, Including Ferroptosis, and Cooperates with the BCL-2 Family to Promote Clonogenic Survival","volume":"21","author":"Wang","year":"2017","journal-title":"Cell Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Alqahtani, A., Ayesh, H.S.K., and Halawani, H. (2019). PIK3CA Gene Mutations in Solid Malignancies: Association with Clinicopathological Parameters and Prognosis. Cancers, 12.","DOI":"10.3390\/cancers12010093"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K\u2013AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"48ps45","DOI":"10.1126\/scitranslmed.3001251","article-title":"Targeting a Common Collaborator in Cancer Development","volume":"2","author":"Myers","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ccr.2012.05.016","article-title":"Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming","volume":"22","author":"Mitsuishi","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_158","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_159","doi-asserted-by":"crossref","first-page":"30691","DOI":"10.18632\/oncotarget.8749","article-title":"PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1158\/0008-5472.CAN-03-2904","article-title":"Akt Stimulates Aerobic Glycolysis in Cancer Cells","volume":"64","author":"Elstrom","year":"2004","journal-title":"Cancer Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.cell.2007.06.009","article-title":"AKT\/PKB signaling: Navigating downstream","volume":"129","author":"Manning","year":"2007","journal-title":"Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"25227","DOI":"10.1074\/jbc.M114.554881","article-title":"Akt-dependent activation of mTORC1 complex involves phosphorylation of mTOR (mammalian target of rapamycin) by I\u03baB kinase \u03b1 (IKK\u03b1)","volume":"289","author":"Dan","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.1128\/MCB.23.20.7315-7328.2003","article-title":"Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival","volume":"23","author":"Rathmell","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1158\/1078-0432.CCR-14-1432","article-title":"HER2 as a therapeutic target in head and neck squamous cell carcinoma","volume":"21","author":"Pollock","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.cell.2017.02.004","article-title":"mTOR Signaling in Growth, Metabolism, and Disease","volume":"168","author":"Saxton","year":"2017","journal-title":"Cell"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1186\/s13046-019-1309-6","article-title":"Effects of hyperglycemia on the progression of tumor diseases","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"e2037","DOI":"10.1038\/cddis.2015.381","article-title":"Obesity and cancer, a case for insulin signaling","volume":"6","author":"Poloz","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1158\/2159-8290.CD-16-0127","article-title":"Role of KEAP1\/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance","volume":"7","author":"Jeong","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/1759-7714.12640","article-title":"Nrf2 and Keap1 abnormalities in esophageal squamous cell carcinoma and association with the effect of chemoradiotherapy","volume":"9","author":"Zhang","year":"2018","journal-title":"Thorac. Cancer"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"12846","DOI":"10.1038\/s41598-018-31281-0","article-title":"A catalogue of somatic NRF2 gain-of-function mutations in cancer","volume":"8","author":"Kerins","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/path.2653","article-title":"Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin","volume":"220","author":"Kim","year":"2010","journal-title":"J. Pathol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.cell.2015.01.043","article-title":"TGF-\u03b2 promotes heterogeneity and drug resistance in squamous cell carcinoma","volume":"160","author":"Oshimori","year":"2015","journal-title":"Cell"},{"key":"ref_174","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_175","doi-asserted-by":"crossref","first-page":"4817","DOI":"10.1158\/0008-5472.CAN-15-0614","article-title":"Nrf2 Activation Promotes Keratinocyte Survival during Early Skin Carcinogenesis via Metabolic Alterations","volume":"75","author":"Rolfs","year":"2015","journal-title":"Cancer Res."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jdv.14151","article-title":"From actinic keratosis to squamous cell carcinoma: Pathophysiology revisited","volume":"31","author":"Figueras","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Jemal, A., Ward, E.M., Johnson, C.J., Cronin, K.A., Ma, J., Ryerson, B., Mariotto, A., Lake, A.J., Wilson, R., and Sherman, R.L. (2017). Annual Report to the Nation on the Status of Cancer, 1975-2014, Featuring Survival. J. Natl. Cancer Inst., 109.","DOI":"10.1093\/jnci\/djx030"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1056\/NEJMoa032646","article-title":"Postoperative Concurrent Radiotherapy and Chemotherapy for High-Risk Squamous-Cell Carcinoma of the Head and Neck","volume":"350","author":"Cooper","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3389\/fonc.2018.00005","article-title":"Before or After: Evolving Neoadjuvant Approaches to Locally Advanced Non-Small Cell Lung Cancer","volume":"8","author":"Lewis","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1056\/NEJMoa1112088","article-title":"Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer","volume":"366","author":"Hulshof","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_181","first-page":"524","article-title":"Treatment of advanced squamous cell carcinoma of the lung: A review","volume":"4","author":"Derman","year":"2015","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"815","DOI":"10.3389\/fonc.2019.00815","article-title":"Best Practice in Systemic Therapy for Head and Neck Squamous Cell Carcinoma","volume":"9","author":"Oosting","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1056\/NEJMra1314530","article-title":"Esophageal Carcinoma","volume":"371","author":"Rustgi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jaad.2017.10.007","article-title":"Guidelines of care for the management of cutaneous squamous cell carcinoma","volume":"78","author":"Kim","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Huang, Z.H., Ma, X.W., Zhang, J., Li, X., Lai, N.L., and Zhang, S.X. (2018). Cetuximab for esophageal cancer: An updated meta-analysis of randomized controlled trials. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5040-z"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1200\/JCO.2010.34.1735","article-title":"Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin","volume":"29","author":"Maubec","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/S0140-6736(09)60569-9","article-title":"Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): An open-label randomised phase III trial","volume":"373","author":"Pirker","year":"2009","journal-title":"Lancet"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"3266","DOI":"10.1200\/JCO.19.00555","article-title":"Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer","volume":"37","author":"Argiris","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/S0140-6736(17)31607-0","article-title":"Bevacizumab for advanced cervical cancer: Final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)","volume":"390","author":"Tewari","year":"2017","journal-title":"Lancet"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"e341S","DOI":"10.1378\/chest.12-2361","article-title":"Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines","volume":"143","author":"Socinski","year":"2013","journal-title":"Chest"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0140-6736(18)31999-8","article-title":"Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): A randomised, open-label, phase 3 study","volume":"393","author":"Cohen","year":"2019","journal-title":"Lancet"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.1200\/JCO.2019.37.15_suppl.4010","article-title":"Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase 3 KEYNOTE-181 study","volume":"37","author":"Shah","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"TPS9598","DOI":"10.1200\/JCO.2019.37.15_suppl.TPS9598","article-title":"KEYNOTE-629: Phase 2 study of pembrolizumab for recurrent\/metastatic or locally advanced unresectable cutaneous squamous cell carcinoma (cSCC)","volume":"37","author":"Grob","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.18.01265","article-title":"Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study","volume":"37","author":"Chung","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1056\/NEJMoa1810865","article-title":"Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer","volume":"379","author":"Luft","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e192535","DOI":"10.1001\/jamanetworkopen.2019.2535","article-title":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","volume":"2","author":"Haslam","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"e1600200","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fonc.2020.00281","article-title":"Metabolic Plasticity in Chemotherapy Resistance","volume":"10","author":"Desbats","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.chembiol.2017.08.028","article-title":"Targeting Metabolism for Cancer Therapy","volume":"24","author":"Luengo","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"3364","DOI":"10.1158\/0008-5472.CAN-06-3717","article-title":"2-Deoxy-D-glucose combined with cisplatin enhances cytotoxicity via metabolic oxidative stress in human head and neck cancer cells","volume":"67","author":"Simons","year":"2007","journal-title":"Cancer Res."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41586-018-0343-4","article-title":"Suppression of insulin feedback enhances the efficacy of PI3K inhibitors","volume":"560","author":"Hopkins","year":"2018","journal-title":"Nature"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41568-019-0135-7","article-title":"Targeting cancer vulnerabilities with high-dose vitamin C","volume":"19","author":"Ngo","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"13604","DOI":"10.1073\/pnas.0506390102","article-title":"Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues","volume":"102","author":"Chen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ccell.2017.02.018","article-title":"O(2)(\u22c5-) and H(2)O(2)-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate","volume":"31","author":"Schoenfeld","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1038\/s41467-020-16243-3","article-title":"Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers","volume":"11","author":"Raucci","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1126\/science.aaa5004","article-title":"Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH","volume":"350","author":"Yun","year":"2015","journal-title":"Science"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.7150\/thno.21745","article-title":"Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation","volume":"8","author":"Lu","year":"2018","journal-title":"Theranostics"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1074\/jbc.M113.538157","article-title":"The hypoxia-inducible factor renders cancer cells more sensitive to vitamin C-induced toxicity","volume":"289","author":"Tian","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3389\/fonc.2020.00976","article-title":"Vitamin C Promotes Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma","volume":"10","author":"Zhou","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Magr\u00ec, A., Germano, G., Lorenzato, A., Lamba, S., Chil\u00e0, R., Montone, M., Amodio, V., Ceruti, T., Sassi, F., and Arena, S. (2020). High-dose vitamin C enhances cancer immunotherapy. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aay8707"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.3389\/fphys.2018.01182","article-title":"Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge","volume":"9","author":"Carr","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1073\/pnas.1014275108","article-title":"Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism","volume":"108","author":"Ren","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_213","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_214","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.freeradbiomed.2016.12.041","article-title":"Halofuginone enhances the chemo-sensitivity of cancer cells by suppressing NRF2 accumulation","volume":"103","author":"Tsuchida","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tibs.2010.05.003","article-title":"Glutamine addiction: A new therapeutic target in cancer","volume":"35","author":"Wise","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S0016-5085(00)70417-3","article-title":"Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Raf-independent mechanism","volume":"118","author":"Rhoads","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1200\/jco.2015.33.15_suppl.2512","article-title":"Safety and tolerability of increasing doses of CB-839, a first-in-class, orally administered small molecule inhibitor of glutaminase, in solid tumors","volume":"33","author":"Harding","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3233\/KCA-180043","article-title":"The \u2019Achilles Heel\u2019 of Metabolism in Renal Cell Carcinoma: Glutaminase Inhibition as a Rational Treatment Strategy","volume":"3","author":"Hoerner","year":"2019","journal-title":"Kidney Cancer"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1200\/JCO.2019.37.4_suppl.574","article-title":"CB-839, panitumumab, and irinotecan in RAS wildtype (WT) metastatic colorectal cancer (mCRC): Phase I results","volume":"37","author":"Ciombor","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"TPS682","DOI":"10.1200\/JCO.2019.37.7_suppl.TPS682","article-title":"CANTATA: Randomized, international, double-blind study of CB-839 plus cabozantinib versus cabozantinib plus placebo in patients with metastatic renal cell carcinoma","volume":"37","author":"Tannir","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/nm.4464","article-title":"Pharmacological blockade of ASCT2-dependent glutamine transport leads to antitumor efficacy in preclinical models","volume":"24","author":"Schulte","year":"2018","journal-title":"Nat. Med."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Lu, H., Lu, Y., Xie, Y., Qiu, S., Li, X., and Fan, Z. (2019). Rational combination with PDK1 inhibition overcomes cetuximab resistance in head and neck squamous cell carcinoma. JCI Insight, 4.","DOI":"10.1172\/jci.insight.131106"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/606\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:35:32Z","timestamp":1760160932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/3\/606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,9]]},"references-count":222,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["cells10030606"],"URL":"https:\/\/doi.org\/10.3390\/cells10030606","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,9]]}}}