{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:58:53Z","timestamp":1774317533957,"version":"3.50.1"},"reference-count":164,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K\/AKT\/mTOR, TP53, RB, and the WNT\/\u03b2-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification.<\/jats:p>","DOI":"10.3390\/biology14070842","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T14:22:36Z","timestamp":1752243756000},"page":"842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4204-2981","authenticated-orcid":false,"given":"Leonor","family":"Barroso","sequence":"first","affiliation":[{"name":"Maxillofacial Surgery Department, Unidade Local de Sa\u00fade de Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Pedro","family":"Veiga","sequence":"additional","affiliation":[{"name":"Institute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-2670","authenticated-orcid":false,"given":"Joana Barbosa","family":"Melo","sequence":"additional","affiliation":[{"name":"Institute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB) and Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Isabel Marques","family":"Carreira","sequence":"additional","affiliation":[{"name":"Institute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB) and Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6096-8705","authenticated-orcid":false,"given":"Ilda Patr\u00edcia","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR) and Center of Investigation on Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB) and Clinical Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21037\/ace.2020.01.01","article-title":"Biological and Epidemiologic Updates on Lip and Oral Cavity Cancers","volume":"4","author":"Nocini","year":"2020","journal-title":"Ann. Cancer Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105451","DOI":"10.1016\/j.oraloncology.2021.105451","article-title":"Overview of Oral Cavity Squamous Cell Carcinoma: Risk Factors, Mechanisms, and Diagnostics","volume":"121","author":"Chamoli","year":"2021","journal-title":"Oral Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and Injuries for 195 Countries and Territories, 1990\u20132017: A Systematic Analysis for the Global Burden of Disease Study 2017","volume":"392","author":"James","year":"2018","journal-title":"Lancet"},{"key":"ref_5","unstructured":"(2025, February 12). International Agency for Research on Cancer. Available online: https:\/\/www.iarc.who.int\/."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41572-020-00224-3","article-title":"Head and Neck Squamous Cell Carcinoma","volume":"6","author":"Johnson","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jcms.2017.10.019","article-title":"The Localization and Risk Factors of Squamous Cell Carcinoma in the Oral Cavity: A Retrospective Study of 1501 Cases","volume":"46","author":"Sundermann","year":"2018","journal-title":"J. Cranio Maxillofac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2011\/525976","article-title":"Smoking, Alcohol, and Betel Quid and Oral Cancer: A Prospective Cohort Study","volume":"2011","author":"Lin","year":"2011","journal-title":"J. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/aje\/kww075","article-title":"Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the Inhance Consortium","volume":"184","author":"Wyss","year":"2016","journal-title":"Am. J. Epidemiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/jnci\/djk179","article-title":"Alcohol Drinking in Never Users of Tobacco, Cigarette Smoking in Never Drinkers, and the Risk of Head and Neck Cancer: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium","volume":"99","author":"Hashibe","year":"2007","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_11","first-page":"3282","article-title":"Smoking and Drinking in Relation to Oral and Pharyngeal Cancer","volume":"48","author":"Blot","year":"1988","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.canep.2018.10.014","article-title":"Incidence and Mortality Trends in Oral and Oropharyngeal Cancers in China, 2005\u20132013","volume":"57","author":"Zhang","year":"2018","journal-title":"Cancer Epidemiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/s41415-022-5166-x","article-title":"Reviewing the Epidemiology of Head and Neck Cancer: Definitions, Trends and Risk Factors","volume":"233","author":"Gormley","year":"2022","journal-title":"Br. Dent. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40348-014-0009-8","article-title":"Fanconi Anemia: Young Patients at High Risk for Squamous Cell Carcinoma","volume":"1","author":"Velleuer","year":"2014","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s12105-022-01414-z","article-title":"Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Familial Tumor Syndromes","volume":"16","author":"Lazar","year":"2022","journal-title":"Head Neck Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"825266","DOI":"10.3389\/fphar.2022.825266","article-title":"Oral Potentially Malignant Disorders: Etiology, Pathogenesis, and Transformation Into Oral Cancer","volume":"13","author":"Kumari","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Warnakulasuriya, S., Kujan, O., Aguirre-Urizar, J.M., Bagan, J.V., \u00c1ngel Gonz\u00e1lez-Moles, M., Kerr, A.R., Lodi, G., Mello, F.W., Monteiro, L., and Ogden, G.R. (2021). Oral Potentially Malignant Disorders: Nomenclature and Classification, LAP Lambert Academic Publishing.","DOI":"10.1111\/ODI.13704\/v2\/response1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/hed.26006","article-title":"Potentially Malignant Disorders of the Oral Cavity and Oral Dysplasia: A Systematic Review and Meta-Analysis of Malignant Transformation Rate by Subtype","volume":"42","author":"Iocca","year":"2020","journal-title":"Head Neck"},{"key":"ref_19","unstructured":"(2025, February 12). NCCN Guidelines. Available online: www.nccn.org\/guidelines."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"941750","DOI":"10.3389\/fcell.2022.941750","article-title":"Current Status and Perspective of Tumor Immunotherapy for Head and Neck Squamous Cell Carcinoma","volume":"10","author":"Yu","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_21","unstructured":"(2025, February 14). Oral Cavity (Mouth) and Oropharyngeal (Throat) Cancer. Available online: www.cancer.org."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1002\/lary.27315","article-title":"Changing Prognosis of Oral Cancer: An Analysis of Survival and Treatment between 1973 and 2014","volume":"128","author":"Cheraghlou","year":"2018","journal-title":"Laryngoscope"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1002\/cncr.28588","article-title":"Causes of Death in Long-Term Survivors of Head and Neck Cancer","volume":"120","author":"Baxi","year":"2014","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1002\/hed.21977","article-title":"Second, Third, and Fourth Head and Neck Tumors. A Progressive Decrease in Survival","volume":"34","author":"Venegas","year":"2012","journal-title":"Head Neck"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/hed.21348","article-title":"Risk of Third and Fourth Tumors in Patients with Head and Neck Cancer","volume":"32","author":"Quer","year":"2010","journal-title":"Head Neck"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1002\/cncr.31675","article-title":"Suicide Risk among Cancer Survivors: Head and Neck versus Other Cancers","volume":"124","author":"Simpson","year":"2018","journal-title":"Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/j.1749-4486.2006.01188.x","article-title":"Deterioration in Quality-of-Life of Late (10-Year) Survivors of Head and Neck Cancer","volume":"31","author":"Mehanna","year":"2006","journal-title":"Clin. Otolaryngol."},{"key":"ref_28","first-page":"1727","article-title":"A Genetic Explanation of Slaughter\u2019s Concept of Field Cancerization: Evidence and Clinical Implications","volume":"63","author":"Braakhuis","year":"2003","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/nrc.2017.102","article-title":"An Evolutionary Perspective on Field Cancerization","volume":"18","author":"Curtius","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/1097-0142(195309)6:5<963::AID-CNCR2820060515>3.0.CO;2-Q","article-title":"Field Cancerization in Oral Stratified Squamous Epithelium; Clinical Implications of Multicentric Origin","volume":"6","author":"Slaughter","year":"1953","journal-title":"Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/154411130301400506","article-title":"The Molecular Biology of Mucosal Field Cancerization of the Head and Neck","volume":"14","author":"Ha","year":"2003","journal-title":"Crit. Rev. Oral. Biol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1002\/path.1285","article-title":"Comparative Molecular and Histological Grading of Epithelial Dysplasia of the Oral Cavity and the Oropharynx","volume":"199","author":"Tabor","year":"2003","journal-title":"J. Pathol."},{"key":"ref_33","first-page":"1523","article-title":"Persistence of Genetically Altered Fields in Head and Neck Cancer Patients: Biological and Clinical Implications","volume":"7","author":"Tabor","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"105544","DOI":"10.1016\/j.archoralbio.2022.105544","article-title":"Occurrence of Field Cancerization in Clinically Normal Oral Mucosa: A Systematic Review and Meta-Analysis","volume":"143","author":"Tucunduva","year":"2022","journal-title":"Arch. Oral Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"368","DOI":"10.32074\/1591-951X-N838","article-title":"DNA Methylation Analysis from Oral Brushing Reveals a Field Cancerization Effect in Proliferative Verrucous Leukoplakia","volume":"116","author":"Gabusi","year":"2024","journal-title":"Pathologica"},{"key":"ref_36","first-page":"13","article-title":"Oral Field Cancerization: An Update on Current Concepts","volume":"8","author":"Mohan","year":"2014","journal-title":"Oncol. Rev."},{"key":"ref_37","first-page":"60","article-title":"Oral Field Cancerization: History and Future Perspectives","volume":"109","author":"Gabusi","year":"2017","journal-title":"Pathologica"},{"key":"ref_38","first-page":"249","article-title":"Oral Field Cancerization: Carcinogen-Induced Independent Events or Micrometastatic Deposits?","volume":"9","author":"Slootweg","year":"2000","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.oraloncology.2015.04.006","article-title":"Cancer Stem Cells and Field Cancerization of Oral Squamous Cell Carcinoma","volume":"51","author":"Simple","year":"2015","journal-title":"Oral. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1001786","DOI":"10.1371\/journal.pmed.1001786","article-title":"Intra-Tumor Genetic Heterogeneity and Mortality in Head and Neck Cancer: Analysis of Data from The Cancer Genome Atlas","volume":"12","author":"Mroz","year":"2015","journal-title":"PLoS Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/cncr.30430","article-title":"The Challenges of Tumor Genetic Diversity","volume":"123","author":"Mroz","year":"2017","journal-title":"Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00428-019-02656-z","article-title":"Prognostic Impact of Intra-Field Heterogeneity in Oral Squamous Cell Carcinoma","volume":"476","author":"Gabusi","year":"2020","journal-title":"Virchows Arch."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1002\/cncr.28150","article-title":"High Intratumor Genetic Heterogeneity Is Related to Worse Outcome in Patients with Head and Neck Squamous Cell Carcinoma","volume":"119","author":"Mroz","year":"2013","journal-title":"Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12105-015-0617-1","article-title":"Mutant Allele Tumor Heterogeneity (MATH) and Head and Neck Squamous Cell Carcinoma","volume":"9","author":"Rocco","year":"2015","journal-title":"Head Neck Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.joms.2018.09.014","article-title":"Intratumoral Heterogeneity in Recurrent Metastatic Squamous Cell Carcinoma of the Oral Cavity: New Perspectives Afforded by Multiregion DNA Sequencing and MtDNA Analysis","volume":"77","author":"Gabusi","year":"2019","journal-title":"J. Oral. Maxillofac. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1136\/mp.53.4.165","article-title":"Reviews Molecular Pathogenesis of Oral Squamous Carcinoma","volume":"53","author":"Williams","year":"2000","journal-title":"Mol Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9135","DOI":"10.1007\/s11033-020-05927-0","article-title":"Genetic Alterations and Clinical Dimensions of Oral Cancer: A Review","volume":"47","author":"Karunakaran","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Roda, D., Veiga, P., Melo, J.B., Carreira, I.M., and Ribeiro, I.P. (2024). Principles in the Management of Glioblastoma. Genes, 15.","DOI":"10.3390\/genes15040501"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.7150\/ijms.94566","article-title":"PI3K\/AKT Signaling Pathway Mediated Autophagy in Oral Carcinoma\u2014A Comprehensive Review","volume":"21","author":"Rajendran","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Harsha, C., Banik, K., Ang, H.L., Girisa, S., Vikkurthi, R., Parama, D., Rana, V., Shabnam, B., Khatoon, E., and Kumar, A.P. (2020). Targeting AKT\/MTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093285"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"C\u00edvico-Ortega, J.L., Gonz\u00e1lez-Ruiz, I., Ramos-Garc\u00eda, P., Cruz-Granados, D., Samayoa-Descamps, V., and Gonz\u00e1lez-Moles, M.\u00c1. (2023). Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511888"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00280-018-3746-x","article-title":"Targeted Disruption of PI3K\/Akt\/MTOR Signaling Pathway, via PI3K Inhibitors, Promotes Growth Inhibitory Effects in Oral Cancer Cells","volume":"83","author":"Aggarwal","year":"2019","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e13558","DOI":"10.1200\/jco.2014.32.15_suppl.e13558","article-title":"Effect of NVP-BEZ235, Dual Phosphatidylinositol 3-Kinase\/Mammalian Target of Rapamycin Inhibitor, on Radiosensitivity of Oral Cancer Cell Line through G2\/M Phase Checkpoint Regulation","volume":"32","author":"Su","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hsu, C.M., Lin, P.M., Lin, H.C., Tsai, Y.T., Tsai, M.S., Li, S.H., Wu, C.Y., Yang, Y.H., Lin, S.F., and Yang, M.Y. (2018). NVP-BEZ235 Attenuated Cell Proliferation and Migration in the Squamous Cell Carcinoma of Oral Cavities and P70s6K Inhibition Mimics Its Effect. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113546"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e0245715","DOI":"10.1371\/journal.pone.0245715","article-title":"PI3k Inhibitors (BKM120 and BYL719) as Radiosensitizers for Head and Neck Squamous Cell Carcinoma during Radiotherapy","volume":"16","author":"Chuang","year":"2021","journal-title":"PLoS ONE"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1111\/jop.12116","article-title":"Cetuximab Inhibits Oral Squamous Cell Carcinoma Invasion and Metastasis via Degradation of Epidermal Growth Factor Receptor","volume":"43","author":"Dai","year":"2014","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3892\/mco.2016.928","article-title":"Cetuximab for the Treatment of Locally Advanced and Recurrent\/Metastatic Oral Cancer: An Investigation of Distant Metastasis","volume":"5","author":"Naruse","year":"2016","journal-title":"Mol. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3892\/or.2020.7674","article-title":"Selective Inhibition of PI3K110\u03b1 as a Novel Therapeutic Strategy for Cetuximab-Resistant Oral Squamous Cell Carcinoma","volume":"44","author":"Tsuchihashi","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_59","first-page":"1379","article-title":"Mitogen-Activated Protein Kinase Signaling Pathway in Oral Cancer (Review)","volume":"15","author":"Peng","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41525-022-00293-1","article-title":"Precision Drugging of the MAPK Pathway in Head and Neck Cancer","volume":"7","author":"Ngan","year":"2022","journal-title":"NPJ Genom. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Cheng, Y., Chen, J., Shi, Y., Fang, X., and Tang, Z. (2022). MAPK Signaling Pathway in Oral Squamous Cell Carcinoma: Biological Function and Targeted Therapy. Cancers, 14.","DOI":"10.3390\/cancers14194625"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3892\/ol.2016.4614","article-title":"JNK1\/2 Expression and Modulation of STAT3 Signaling in Oral Cancer","volume":"12","author":"Gkouveris","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1158\/1078-0432.CCR-16-1469","article-title":"Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial","volume":"23","author":"Uppaluri","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41392-023-01347-1","article-title":"Targeting P53 Pathways: Mechanisms, Structures, and Advances in Therapy","volume":"8","author":"Wang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12935-021-02396-8","article-title":"P53 Signaling in Cancer Progression and Therapy","volume":"21","author":"Marei","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"582","DOI":"10.4103\/jomfp.JOMFP_106_20","article-title":"Expression of P53 at Invasive Front of Oral Squamous Cell Carcinoma and Negative Histopathological Surgical Margins to Establish Correlation at 3-Year Survival","volume":"24","author":"Gawande","year":"2020","journal-title":"J. Oral. Maxillofac. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e006666","DOI":"10.1136\/jitc-2023-006666","article-title":"TP53 Gain-of-Function Mutation Modulates the Immunosuppressive Microenvironment in Non-HPV-Associated Oral Squamous Cell Carcinoma","volume":"11","author":"Shi","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"21695","DOI":"10.1038\/s41598-022-25744-8","article-title":"The Mutational Spectrum in Whole Exon of P53 in Oral Squamous Cell Carcinoma and Its Clinical Implications","volume":"12","author":"Hyodo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1002\/jcb.25592","article-title":"TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response","volume":"117","author":"Zhou","year":"2016","journal-title":"J. Cell. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1158\/1078-0432.CCR-17-0721","article-title":"High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity Squamous Cell Carcinoma","volume":"24","author":"Sandulache","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100614","DOI":"10.1016\/j.modpat.2024.100614","article-title":"Abnormal P53 Immunohistochemical Patterns Are Associated with Regional Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma at Time of Surgery","volume":"37","author":"Lin","year":"2024","journal-title":"Mod. Pathol."},{"key":"ref_72","first-page":"1","article-title":"Phenethyl Isothiocyanate (PEITC) Inhibits the Growth of Human Oral Squamous Carcinoma Hsc-3 Cells through g 0\/g 1 Phase Arrest and Mitochondria-Mediated Apoptotic Cell Death","volume":"2012","author":"Chen","year":"2012","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2014.06.008","article-title":"Phenethyl Isothiocyanate Induces DNA Damage-Associated G2\/M Arrest and Subsequent Apoptosis in Oral Cancer Cells with Varying P53 Mutations","volume":"74","author":"Yeh","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4103\/1735-3327.161427","article-title":"The Expression of Retinoblastoma Tumor Suppressor Protein in Oral Cancers and Precancers: A Clinicopathological Study","volume":"12","author":"Thomas","year":"2015","journal-title":"Dent. Res. J."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Nakajima, R., Shirasawa, M., Fikriyanti, M., Zhao, L., Iwanaga, R., Bradford, A.P., Kurayoshi, K., Araki, K., and Ohtani, K. (2023). Expanding Roles of the E2F-RB-P53 Pathway in Tumor Suppression. Biology, 12.","DOI":"10.3390\/biology12121511"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s13402-014-0173-9","article-title":"Retinoblastoma (RB1) Pocket Domain Mutations and Promoter Hyper-Methylation in Head and Neck Cancer","volume":"37","author":"Sabir","year":"2014","journal-title":"Cell. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1177\/107327480200900502","article-title":"Molecular Genetics of Head and Neck Cancer","volume":"9","author":"Gleich","year":"2002","journal-title":"Cancer Control."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/modpathol.3800387","article-title":"Phenotypic Alterations in Rb Pathway Have More Prognostic Influence than P53 Pathway Proteins in Oral Carcinoma","volume":"18","author":"Jayasurya","year":"2005","journal-title":"Mod. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s12105-021-01317-5","article-title":"RB1, P16, and Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma","volume":"15","author":"Berdugo","year":"2021","journal-title":"Head Neck Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.trecan.2019.03.005","article-title":"Cell Cycle and Beyond: Exploiting New RB1 Controlled Mechanisms for Cancer Therapy","volume":"5","author":"Knudsen","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41392-021-00762-6","article-title":"Wnt\/\u03b2-Catenin Signalling: Function, Biological Mechanisms, and Therapeutic Opportunities","volume":"7","author":"Liu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.sdentj.2021.08.002","article-title":"Wnt Pathway in Oral Cancer: A Review Update","volume":"33","author":"Purwaningsih","year":"2021","journal-title":"Saudi Dent. J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Reyes, M., Flores, T., Betancur, D., Pe\u00f1a-Oyarz\u00fan, D., and Torres, V.A. (2020). Wnt\/\u03b2-Catenin Signaling in Oral Carcinogenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134682"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/S1368-8375(02)00044-1","article-title":"Expression of B-Catenin in Rat Oral Epithelial Dysplasia Induced by 4-Nitroquinoline 1-Oxide","volume":"38","author":"Sato","year":"2002","journal-title":"Oral Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Campolo, M., Scuderi, S.A., Filippone, A., Bova, V., Lombardo, S.P., Colarossi, L., Sava, S., Capra, A.P., De Gaetano, F., and Portelli, M. (2024). EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt\/\u03b2-Catenin Pathway Modulation. Pharmaceuticals, 17.","DOI":"10.3390\/ph17081102"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.oooo.2021.04.004","article-title":"Understanding the Complex Pathogenesis of Oral Cancer: A Comprehensive Review","volume":"132","author":"Georgaki","year":"2021","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e54705","DOI":"10.1371\/journal.pone.0054705","article-title":"Genome Wide Analysis of Chromosomal Alterations in Oral Squamous Cell Carcinomas Revealed over Expression of MGAM and ADAM9","volume":"8","author":"Anwar","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.oraloncology.2007.05.003","article-title":"Chromosomal Imbalances in Oral Squamous Cell Carcinoma. Examination of 31 Cell Lines and Review of the Literature","volume":"44","author":"Reshmi","year":"2008","journal-title":"Oral Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1158\/2159-8290.CD-12-0537","article-title":"Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers","volume":"3","author":"Pickering","year":"2013","journal-title":"Cancer Discov."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/jop.13303","article-title":"Recurrent Copy Number Alterations Involving EGFR, CDKN2A, and CCND1 in Oral Premalignant Lesions","volume":"51","author":"Fehr","year":"2022","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"59113","DOI":"10.18632\/oncotarget.19262","article-title":"Profiling Cancer-Related Gene Mutations in Oral Squamous Cell Carcinoma from Japanese Patients by Targeted Amplicon Sequencing","volume":"8","author":"Nakagaki","year":"2017","journal-title":"Oncotarget"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"870055","DOI":"10.3389\/fonc.2022.870055","article-title":"FAT1 Upregulates in Oral Squamous Cell Carcinoma and Promotes Cell Proliferation via Cell Cycle and DNA Repair","volume":"12","author":"Lan","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mesgari, H., Esmaelian, S., Nasiri, K., Ghasemzadeh, S., Doroudgar, P., and Payandeh, Z. (2023). Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review. Cancers, 15.","DOI":"10.3390\/cancers15235600"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4103\/jomfp.JOMFP_150_17","article-title":"Epigenetics in Oral Squamous Cell Carcinoma","volume":"21","author":"Hema","year":"2017","journal-title":"J. Oral. Maxillofac. Pathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"103399","DOI":"10.1016\/j.critrevonc.2021.103399","article-title":"DNA Methylation in Oral Squamous Cell Carcinoma: From Its Role in Carcinogenesis to Potential Inhibitor Drugs","volume":"164","author":"Flausino","year":"2021","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Irimie, A.I., Ciocan, C., Gulei, D., Mehterov, N., Atanasov, A.G., Dudea, D., and Berindan-Neagoe, I. (2018). Current Insights into Oral Cancer Epigenetics. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030670"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-024-01993-1","article-title":"DNMT1-Targeting Remodeling Global DNA Hypomethylation for Enhanced Tumor Suppression and Circumvented Toxicity in Oral Squamous Cell Carcinoma","volume":"23","author":"Liu","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.oraloncology.2013.08.005","article-title":"Global Analysis of DNA Methylation Changes during Progression of Oral Cancer","volume":"49","author":"Towle","year":"2013","journal-title":"Oral. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13148-019-0715-0","article-title":"Aberrantly Hypermethylated Tumor Suppressor Genes Were Identified in Oral Squamous Cell Carcinoma (OSCC)","volume":"11","author":"Kim","year":"2019","journal-title":"Clin. Epigenetics"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1016\/j.jcms.2018.07.019","article-title":"Promotor Hypermethylated Genes: Prospective Diagnostic Biomarkers in Oral Cancerogenesis","volume":"46","author":"Dvojakovska","year":"2018","journal-title":"J. Cranio Maxillofac. Surg."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.semcancer.2020.07.015","article-title":"Histone Modifications in Epigenetic Regulation of Cancer: Perspectives and Achieved Progress","volume":"83","author":"Neganova","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Ruzic, D., Djokovi\u0107, N., Srdi\u0107-Raji\u0107, T., Echeverria, C., Nikolic, K., and Santibanez, J.F. (2022). Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010209"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1164514","DOI":"10.3389\/fimmu.2023.1164514","article-title":"Inhibition of Histone Deacetylases Attenuates Tumor Progression and Improves Immunotherapy in Breast Cancer","volume":"14","author":"Lian","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"109778","DOI":"10.1016\/j.cbi.2021.109778","article-title":"A Novel HDAC1\/2 Inhibitor Suppresses Colorectal Cancer through Apoptosis Induction and Cell Cycle Regulation","volume":"352","author":"Lee","year":"2022","journal-title":"Chem. Biol. Interact."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4161\/epi.3.6.7273","article-title":"The Role of Histone Deacetylases in Prostate Cancer","volume":"3","author":"Abbas","year":"2008","journal-title":"Epigenetics"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1170207","DOI":"10.3389\/fimmu.2023.1170207","article-title":"HDAC Inhibitors Enhance the Anti-Tumor Effect of Immunotherapies in Hepatocellular Carcinoma","volume":"14","author":"Shen","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Antrobus, J., Mackinnon, B., Melia, E., Hughes, J.R., and Parsons, J.L. (2024). HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair. Cancers, 16.","DOI":"10.3390\/cancers16234108"},{"key":"ref_108","first-page":"1","article-title":"Effect of Valproic Acid on Histone Deacetylase Expression in Oral Cancer (Review)","volume":"27","author":"Wang","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_109","first-page":"6552","article-title":"HDAC Inhibitor Apicidin Suppresses Murine Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo via Inhibiting HDAC8 Expression","volume":"16","author":"Ahn","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/j.oraloncology.2011.07.027","article-title":"Apicidin, a Histone Deaceylase Inhibitor, Induces Both Apoptosis and Autophagy in Human Oral Squamous Carcinoma Cells","volume":"47","author":"Ahn","year":"2011","journal-title":"Oral. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12967-024-05169-9","article-title":"Targeting Histone Deacetylases in Head and Neck Squamous Cell Carcinoma: Molecular Mechanisms and Therapeutic Targets","volume":"22","author":"Xu","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1042\/EBC20200032","article-title":"Non-Coding RNA in Cancer","volume":"65","author":"Yan","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Smolarz, B., Durczy\u0144ski, A., Romanowicz, H., Szy\u0142\u0142o, K., and Hogendorf, P. (2022). MiRNAs in Cancer (Review of Literature). Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052805"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Osan, C., Chira, S., Nutu, A.M., Braicu, C., Baciut, M., Korban, S.S., and Berindan-Neagoe, I. (2021). The Connection between Micrornas and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management. Genes, 12.","DOI":"10.3390\/genes12121989"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e1754","DOI":"10.1002\/wrna.1754","article-title":"Noncoding RNAs in Oral Cancer","volume":"14","author":"Balakittnen","year":"2023","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/odi.13739","article-title":"mu A Variant of H19 Transcript Regulates EMT and Oral Cancer Progression","volume":"28","author":"Zhou","year":"2022","journal-title":"Oral. Dis."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"153112","DOI":"10.1016\/j.prp.2020.153112","article-title":"An Insight into the Roles of PiRNAs and PIWI Proteins in the Diagnosis and Pathogenesis of Oral, Esophageal, and Gastric Cancer","volume":"216","author":"Halajzadeh","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/14756366.2018.1426574","article-title":"Differential Expression of SnoRNAs in Oral Squamous Cell Carcinomas: New Potential Diagnostic Markers","volume":"33","year":"2018","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Crist\u00f3bal, I., Caram\u00e9s, C., Rubio, J., Sanz-Alvarez, M., Luque, M., Madoz-G\u00farpide, J., Rojo, F., and Garc\u00eda-Foncillas, J. (2020). Functional and Clinical Impact of Circrnas in Oral Cancer. Cancers, 12.","DOI":"10.3390\/cancers12041041"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100162","DOI":"10.1016\/j.oor.2024.100162","article-title":"Beyond Tissue: Liquid Biopsy\u2019s Promise in Unmasking Oral Cancer","volume":"9","author":"Deorah","year":"2024","journal-title":"Oral Oncol. Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ijom.2021.08.017","article-title":"The Scope of Liquid Biopsy in the Clinical Management of Oral Cancer","volume":"51","author":"Baby","year":"2022","journal-title":"Int. J. Oral. Maxillofac. Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"103","DOI":"10.17998\/jlc.2022.09.08","article-title":"Liquid Biopsy for Early Detection and Therapeutic Monitoring of Hepatocellular Carcinoma","volume":"22","author":"Choi","year":"2022","journal-title":"J. Liver Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"594","DOI":"10.21037\/tlcr-22-742","article-title":"Current and Future Applications of Liquid Biopsy in Non-Small-Cell Lung Cancer-A Narrative Review","volume":"12","author":"Tomasik","year":"2023","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Gattuso, G., Crimi, S., Lavoro, A., Rizzo, R., Musumarra, G., Gallo, S., Facciponte, F., Paratore, S., Russo, A., and Bordonaro, R. (2022). Liquid Biopsy and Circulating Biomarkers for the Diagnosis of Precancerous and Cancerous Oral Lesions. Noncoding RNA, 8.","DOI":"10.3390\/ncrna8040060"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1097\/PPO.0000000000000311","article-title":"Molecular Profiling of Liquid Biopsy Samples for Precision Medicine","volume":"24","author":"Campos","year":"2018","journal-title":"Cancer J."},{"key":"ref_126","first-page":"87","article-title":"Liquid Biopsy: A Comprehensive Review","volume":"15","author":"Shinde","year":"2024","journal-title":"Oral. Maxillofac. Pathol. J."},{"key":"ref_127","first-page":"e51684","article-title":"Circulating Tumor Cells in Oral Cancer","volume":"16","author":"Sharma","year":"2024","journal-title":"Cureus"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-022-00403-2","article-title":"Detection of Circulating Tumor Cells: Opportunities and Challenges","volume":"10","author":"Ju","year":"2022","journal-title":"Biomark. Res."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Tretyakova, M.S., Menyailo, M.E., Schegoleva, A.A., Bokova, U.A., Larionova, I.V., and Denisov, E.V. (2022). Technologies for Viable Circulating Tumor Cell Isolation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415979"},{"key":"ref_130","first-page":"1","article-title":"Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Tongue Squamous Cell Carcinoma and Its Relationship with Clinical Features and Prognosis: A Retrospective Study","volume":"15","author":"Geng","year":"2024","journal-title":"Discov. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e15541","DOI":"10.1200\/JCO.2020.38.15_suppl.e15541","article-title":"Correlation of CTCs with Disease Progression in Indian Oral Cancer Patients","volume":"38","author":"Khandare","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.oooo.2022.02.018","article-title":"Circulating Tumor Cells as a Predictor for Poor Prognostic Factors and Overall Survival in Treatment Na\u00efve Oral Squamous Cell Carcinoma Patients","volume":"134","author":"Qayyumi","year":"2022","journal-title":"Oral. Surg. Oral. Med. Oral. Pathol. Oral. Radiol."},{"key":"ref_133","first-page":"591","article-title":"Detection of Peripheral Blood Circulating Tumor Cells in Oral Squamous Cell Carcinoma and Its Clinical Significance","volume":"39","author":"Zhang","year":"2021","journal-title":"Hua Xi Kou Qiang Yi Xue Za Zhi\/West. China J. Stomatol."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Telekes, A., and Horv\u00e1th, A. (2022). The Role of Cell-Free DNA in Cancer Treatment Decision Making. Cancers, 14.","DOI":"10.3390\/cancers14246115"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e006013","DOI":"10.1136\/jitc-2022-006013","article-title":"Cell-Free DNA Approaches for Cancer Early Detection and Interception","volume":"11","author":"Medina","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"102595","DOI":"10.1016\/j.ctrv.2023.102595","article-title":"Strategies for Improving Detection of Circulating Tumor DNA Using next Generation Sequencing","volume":"119","author":"Roberto","year":"2023","journal-title":"Cancer Treat. Rev."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Dao, J., Conway, P.J., Subramani, B., Meyyappan, D., Russell, S., and Mahadevan, D. (2023). Using CfDNA and CtDNA as Oncologic Markers: A Path to Clinical Validation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713219"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e766","DOI":"10.1002\/mco2.766","article-title":"Circulating Tumor DNA Methylation Detection as Biomarker and Its Application in Tumor Liquid Biopsy: Advances and Challenges","volume":"5","author":"Li","year":"2024","journal-title":"MedComm"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/s41551-021-00837-3","article-title":"Limitations and Opportunities of Technologies for the Analysis of Cell-Free DNA in Cancer Diagnostics","volume":"6","author":"Song","year":"2022","journal-title":"Nat. Biomed. Eng."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Lin, L.H., Chang, K.W., Kao, S.Y., Cheng, H.W., and Liu, C.J. (2018). Increased Plasma Circulating Cell-Free DNA Could Be a Potential Marker for Oral Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113303"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"106717","DOI":"10.1016\/j.oraloncology.2024.106717","article-title":"Mutation Detection in Saliva from Oral Cancer Patients","volume":"151","author":"Ahmed","year":"2024","journal-title":"Oral. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"101827","DOI":"10.1016\/j.tranon.2023.101827","article-title":"Saliva as a Potential Non-Invasive Liquid Biopsy for Early and Easy Diagnosis\/Prognosis of Head and Neck Cancer","volume":"40","author":"Kumar","year":"2024","journal-title":"Transl. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Rashid, S., Puttagunta, P., Pamulapati, S., Yang, J., Pocha, S., Saba, N.F., and Teng, Y. (2024). Leveraging Saliva for Insights into Head and Neck Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252413514"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/jop.13299","article-title":"Integrity and Quantity of Salivary Cell-Free DNA as a Potential Molecular Biomarker in Oral Cancer: A Preliminary Study","volume":"51","author":"Abalo","year":"2022","journal-title":"J. Oral. Pathol. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"100618","DOI":"10.1016\/j.oor.2024.100618","article-title":"The Role of Liquid Biopsy in Early Detection and Monitoring of Oral Cancer","volume":"11","author":"Devaraji","year":"2024","journal-title":"Oral. Oncol. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s13148-024-01716-9","article-title":"DNA Methylation Markers for Oral Cancer Detection in Non- and Minimally Invasive Samples: A Systematic Review","volume":"16","author":"Salta","year":"2024","journal-title":"Clin. Epigenetics"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1002\/cam4.17","article-title":"Differential Expression of MiRNAs in the Serum of Patients with High-Risk Oral Lesions","volume":"1","author":"MacLellan","year":"2012","journal-title":"Cancer Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/odi.12340","article-title":"Salivary MicroRNAs in Oral Cancer","volume":"21","author":"Zahran","year":"2015","journal-title":"Oral. Dis."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ol.2021.12433","article-title":"Screening and Validation of Plasma Long Non-Coding RNAs as Biomarkers for the Early Diagnosis and Staging of Oral Squamous Cell Carcinoma","volume":"21","author":"Jia","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1186\/s12885-020-07408-w","article-title":"Upregulation of Long Non-Coding RNA LOC284454 May Serve as a New Serum Diagnostic Biomarker for Head and Neck Cancers","volume":"20","author":"Fan","year":"2020","journal-title":"BMC Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Roi, A., Boia, S., Rusu, L.-C., Roi, C.I., Boia, E.R., and Rivi\u0219, M. (2023). Circulating MiRNA as a Biomarker in Oral Cancer Liquid Biopsy. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030965"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3892\/mmr.2012.1254","article-title":"Salivary LncRNA as a Potential Marker for Oral Squamous Cell Carcinoma Diagnosis","volume":"7","author":"Tang","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Irmer, B., Chandrabalan, S., Maas, L., Bleckmann, A., and Menck, K. (2023). Extracellular Vesicles in Liquid Biopsies as Biomarkers for Solid Tumors. Cancers, 15.","DOI":"10.3390\/cancers15041307"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-023-00540-2","article-title":"Extracellular Vesicle-Based Liquid Biopsy Biomarkers and Their Application in Precision Immuno-Oncology","volume":"11","author":"Asleh","year":"2023","journal-title":"Biomark. Res."},{"key":"ref_155","first-page":"80","article-title":"Isolation and Analysis Methods of Extracellular Vesicles (EVs)","volume":"2","author":"Zhao","year":"2021","journal-title":"Extracell. Vesicles Circ. Nucl. Acids"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcancer.2021.01.002","article-title":"Profiling of Extracellular Vesicles in Oral Cancer, from Transcriptomics to Proteomics","volume":"74","author":"Leung","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1021\/acsabm.3c01243","article-title":"Exosomes: A Cutting-Edge Theranostics Tool for Oral Cancer","volume":"7","author":"Kalele","year":"2024","journal-title":"ACS Appl. Bio. Mater."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"110094","DOI":"10.1016\/j.intimp.2023.110094","article-title":"Oral Squamous Cell Carcinoma-Derived EVs Promote Tumor Progression by Regulating Inflammatory Cytokines and the IL-17A-Induced Signaling Pathway","volume":"118","author":"Li","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"112820","DOI":"10.1016\/j.intimp.2024.112820","article-title":"Extracellular Vesicles Reshape the Tumor Microenvironment to Improve Cancer Immunotherapy: Current Knowledge and Future Prospects","volume":"140","author":"Hang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"34838","DOI":"10.18632\/oncotarget.26208","article-title":"Extracellular Vesicles in Oral Squamous Carcinoma Carry Oncogenic MiRNA Profile and Reprogram Monocytes via NF-\u039aB Pathway","volume":"9","author":"Bala","year":"2018","journal-title":"Oncotarget"},{"key":"ref_161","first-page":"2432","article-title":"Exosome-Mediated Transfer from the Tumor Microenvironment Increases TGF\u03b2 Signaling in Squamous Cell Carcinoma","volume":"8","author":"Languino","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"15252","DOI":"10.18632\/oncotarget.14862","article-title":"Selective Extracellular Vesicle Exclusion of MiR-142-3p by Oral Cancer Cells Promotes Both Internal and Extracellular Malignant Phenotypes","volume":"8","author":"Dickman","year":"2017","journal-title":"Oncotarget"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"15781","DOI":"10.1007\/s00432-023-05343-4","article-title":"Exploring Salivary Exosomes as Early Predictors of Oral Cancer in Susceptible Tobacco Consumers: Noninvasive Diagnostic and Prognostic Applications","volume":"149","author":"Bano","year":"2023","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41368-023-00274-9","article-title":"Emerging Roles of Exosomes in Oral Diseases Progression","volume":"16","author":"Wang","year":"2024","journal-title":"Int. J. Oral. 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