Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment
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 aerodigest...
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2025-07-01
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| author | Leonor Barroso Pedro Veiga Joana Barbosa Melo Isabel Marques Carreira Ilda Patrícia Ribeiro |
| author_facet | Leonor Barroso Pedro Veiga Joana Barbosa Melo Isabel Marques Carreira Ilda Patrícia Ribeiro |
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| description | 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/β-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 <i>TP53</i>, <i>CCND1</i>, <i>CTTN</i>, <i>CDKN2A</i>, <i>EGFR</i>, <i>HRAS</i>, <i>PI3K</i>, <i>ADAM9</i>, <i>MGAM</i>, <i>SIRPB1</i>, and <i>FAT1</i>, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of <i>CDKN2A</i>, <i>APC</i>, <i>MGMT</i>, <i>PTEN</i>, <i>CDH1</i>, <i>TFP12</i>, <i>SOX17</i>, <i>GATA4</i>, <i>ECAD</i>, <i>MGMT</i>, and <i>DAPK</i>. 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. |
| format | Article |
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| spelling | doaj-art-48cb1519423f452a8d4beab88b868ea52025-07-25T13:15:09ZengMDPI AGBiology2079-77372025-07-0114784210.3390/biology14070842Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and TreatmentLeonor Barroso0Pedro Veiga1Joana Barbosa Melo2Isabel Marques Carreira3Ilda Patrícia Ribeiro4Maxillofacial Surgery Department, Unidade Local de Saúde de Coimbra, 3000-075 Coimbra, PortugalInstitute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalInstitute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalInstitute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalInstitute of Cellular and Molecular Biology, Cytogenetics and Genomics Laboratory, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, PortugalOral 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/β-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 <i>TP53</i>, <i>CCND1</i>, <i>CTTN</i>, <i>CDKN2A</i>, <i>EGFR</i>, <i>HRAS</i>, <i>PI3K</i>, <i>ADAM9</i>, <i>MGAM</i>, <i>SIRPB1</i>, and <i>FAT1</i>, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of <i>CDKN2A</i>, <i>APC</i>, <i>MGMT</i>, <i>PTEN</i>, <i>CDH1</i>, <i>TFP12</i>, <i>SOX17</i>, <i>GATA4</i>, <i>ECAD</i>, <i>MGMT</i>, and <i>DAPK</i>. 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.https://www.mdpi.com/2079-7737/14/7/842oral cancersquamous cell carcinomaliquid biopsiessignaling pathwaysgenetic biomarkerscirculating tumor DNA |
| spellingShingle | Leonor Barroso Pedro Veiga Joana Barbosa Melo Isabel Marques Carreira Ilda Patrícia Ribeiro Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment Biology oral cancer squamous cell carcinoma liquid biopsies signaling pathways genetic biomarkers circulating tumor DNA |
| title | Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment |
| title_full | Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment |
| title_fullStr | Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment |
| title_full_unstemmed | Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment |
| title_short | Molecular and Genetic Pathogenesis of Oral Cancer: A Basis for Customized Diagnosis and Treatment |
| title_sort | molecular and genetic pathogenesis of oral cancer a basis for customized diagnosis and treatment |
| topic | oral cancer squamous cell carcinoma liquid biopsies signaling pathways genetic biomarkers circulating tumor DNA |
| url | https://www.mdpi.com/2079-7737/14/7/842 |
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