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Search Results (1,345)

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Keywords = oral squamous cell carcinoma

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16 pages, 1194 KiB  
Systematic Review
Artificial Intelligence in the Diagnosis of Tongue Cancer: A Systematic Review with Meta-Analysis
by Seorin Jeong, Hae-In Choi, Keon-Il Yang, Jin Soo Kim, Ji-Won Ryu and Hyun-Jeong Park
Biomedicines 2025, 13(8), 1849; https://doi.org/10.3390/biomedicines13081849 - 30 Jul 2025
Viewed by 268
Abstract
Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and [...] Read more.
Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article
(This article belongs to the Special Issue Recent Advances in Oral Medicine—2nd Edition)
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26 pages, 2478 KiB  
Article
Clinical Relevance of FOXP3, PD-L1, PD-1, and miR-155 Gene Expression and Genetic Variants in HPV-Negative Oral Carcinomas
by Nemanja Ivkovic, Debora Misic, Ruzica Kozomara, Sasa Jovic, Ahmad Sami, Gordana Velikic, Srboljub Stosic and Gordana Supic
Int. J. Mol. Sci. 2025, 26(15), 7218; https://doi.org/10.3390/ijms26157218 - 25 Jul 2025
Viewed by 309
Abstract
PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 [...] Read more.
PD-L1, PD-1, FOXP3, and miR-155 are emerging as key modulators of immune evasion and progression of oral squamous cell carcinoma (OSCC). This study investigated the clinical relevance of their gene expression and variants in HPV-negative OSCC. Bulk-tissue mRNA expression was evaluated in 70 patients, while variants in PD-1 (rs36084323), PD-L1 (rs822336, rs4143815, copy number variation), FOXP3 (rs3761548, rs2232365), and miR-155 (rs767649) were assessed in 134 patients. Expression data were validated using the TCGA cohort of 222 HPV-negative OSCC cases. Low FOXP3 expression was significantly associated with tumor stage (MMA: p = 0.028, TCGA: p = 0.025) and poor overall survival (MMA: p = 0.0004, TCGA: p = 0.019) in both cohorts. Declining FOXP3 expression correlated with advancing tumor stages, and low FOXP3 expression was significantly associated with poor survival in advanced stage III–IV tumors (MMA: p = 0.001, TCGA: p = 0.015), but not early-stage tumors. High miR-155 expression was associated with recurrence (p = 0.002) and poor survival in the MMA (p = 0.007), but not TCGA cohort. MiR-155 rs767649 was associated with alcohol consumption (p = 0.018). These findings point to FOXP3 and miR-155 as potential prognostic biomarkers for HPV-negative OSCC. Stage-specific FOXP3 expression suggests a dynamic immunoregulatory role, with implications for optimizing immunotherapy timing. Further studies are warranted to resolve cellular context and stage-adapted immune interventions in HPV-negative OSCC. Full article
(This article belongs to the Special Issue Oral Cancer and Disease in Humans and Animals)
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19 pages, 957 KiB  
Article
Clinicopathologic Predictors of Survival Following Oral Cancer Surgery: A Retrospective Cohort Study
by Katarzyna Stawarz, Karolina Bieńkowska-Pluta, Adam Galazka, Anna Gorzelnik, Monika Durzynska, Magdalena Misiak-Galazka, Grzegorz Stawarz and Jakub Zwolinski
Cancers 2025, 17(15), 2454; https://doi.org/10.3390/cancers17152454 - 24 Jul 2025
Viewed by 342
Abstract
Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance [...] Read more.
Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article
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40 pages, 1654 KiB  
Review
Bioactive Plant-Derived Compounds as Novel Perspectives in Oral Cancer Alternative Therapy
by Gabriela Mitea, Verginica Schröder and Irina Mihaela Iancu
Pharmaceuticals 2025, 18(8), 1098; https://doi.org/10.3390/ph18081098 - 24 Jul 2025
Viewed by 433
Abstract
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article
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16 pages, 2052 KiB  
Article
Prognostic Implications of T Cell Receptor Repertoire Diversity in Cervical Lymph Nodes of Oral Squamous Cell Carcinoma Patients
by Kenichi Kumagai, Yoshiki Hamada, Akihisa Horie, Yudai Shimizu, Yoshihiro Ohashi, Reo Aoki, Taiki Suzuki, Koji Kawaguchi, Akihiro Kuroda, Takahiro Tsujikawa, Kazuto Hoshi and Kazuhiro Kakimi
Int. J. Mol. Sci. 2025, 26(15), 7073; https://doi.org/10.3390/ijms26157073 - 23 Jul 2025
Viewed by 219
Abstract
The immune landscape of tumor-draining lymph nodes (TDLNs) plays a critical role in shaping antitumor responses and influencing prognosis in oral squamous cell carcinoma (OSCC). Among patients with lymph node (LN) metastasis, clinical outcomes vary widely, yet reliable biomarkers for prognostic stratification remain [...] Read more.
The immune landscape of tumor-draining lymph nodes (TDLNs) plays a critical role in shaping antitumor responses and influencing prognosis in oral squamous cell carcinoma (OSCC). Among patients with lymph node (LN) metastasis, clinical outcomes vary widely, yet reliable biomarkers for prognostic stratification remain limited. This study aimed to identify immune features in tumors and LNs that differentiate between favorable and poor outcomes in OSCC patients with nodal metastasis. We analyzed T cell receptor (TCR) CDR3 repertoires and the expression of immune-related genes in primary tumors and paired sentinel LNs from OSCC patients who underwent tumor resection and lymphadenectomy. Patients were divided into three groups: Group A (no nodal metastasis), Group B1 (metastasis without recurrence), and Group B2 (metastasis with recurrence). TCR diversity was assessed using the Shannon index. The expression of immune-related genes (e.g., CD3E, CD4, CD8B, FOXP3, CTLA4, IL2, IL4) was measured by quantitative PCR and normalized to GAPDH. TCR diversity was lower in tumors than in non-metastatic LNs, reflecting clonal expansion. Metastatic LNs exhibited tumor-like diversity, suggesting infiltration by tumor-reactive clones. Tumor gene expression did not differ across groups, but LNs from metastatic cases showed the reduced expression of several immune genes. Notably, CD3E, CD8B, CTLA4, IL2, and IL4 distinguished B1 from B2. The immune profiling of LNs offers superior prognostic value over tumor analysis in OSCC patients with LN metastasis. LN-based evaluation may aid in postoperative risk stratification and personalized postoperative management and could inform decisions regarding adjuvant therapy and follow-up strategies. Full article
(This article belongs to the Section Molecular Biology)
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21 pages, 810 KiB  
Review
Molecular Crosstalk and Therapeutic Synergy: Tyrosine Kinase Inhibitors and Cannabidiol in Oral Cancer Treatment
by Zainab Saad Ghafil AlRaheem, Thao T. Le, Ali Seyfoddin and Yan Li
Curr. Issues Mol. Biol. 2025, 47(8), 584; https://doi.org/10.3390/cimb47080584 - 23 Jul 2025
Viewed by 304
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies. Full article
(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery)
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14 pages, 9728 KiB  
Article
Combined Model of Tumor–Stroma Ratio and Tumor Budding Are Not Associated with Tumor Recurrence or Metastasis in Oral Squamous Cell Carcinoma Patients
by Drago Boščić, Emili Dragaš, Andro Košec, Goran Geber, Čedna Tomasović-Lončarić and Davor Vagić
Diagnostics 2025, 15(15), 1844; https://doi.org/10.3390/diagnostics15151844 - 22 Jul 2025
Viewed by 276
Abstract
Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. [...] Read more.
Histopathological grading of oral squamous cell carcinoma is currently based on differentiation of cells, while additional histological parameters, such as the tumor–stroma ratio (TSR), tumor budding (TB), or the combined TSR/tumor budding model could better assess tumor biological behavior and monitoring of patients. Background/Objectives: To integrate risk factors associated with tumor progression: the TSR, TB and TSR/tumor budding model, whose prognostic significance in oral cancer has not yet been evaluated. Methods: An observational cohort retrospective study assembled according to STROBE guidelines on histological materials from 196 patients with invasive squamous cell carcinoma of the oral cavity. The goal of the analysis was to evaluate the association between the tumor stroma ratio, tumor budding, and the combined model of TSR/TB with the clinical and pathologic features of patients with squamous cell carcinoma of the oral cavity and to determine the prognostic value of this model in relation to disease-free survival (DFS) Results: The analysis did not show that the tumor stroma ratio (TSR), tumor budding, and the combined model of TSR/tumor budding were statistically significantly associated with the occurrence of metastatic disease at the start of treatment or during postoperative follow-up, but confirmed the value of depth-of-invasion (DOI) as a negative prognostic factor (HR 15.3, p < 0.001). Conclusions: The TSR, TB, and the combined TSR/TB model were not found to be statistically significant predictors for the disease progression in the Cox regression survival analysis but were found to have a significant correlation with known negative prognostic factors: DOI, neural invasion, and T category. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Management of Oral Disorders)
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16 pages, 2557 KiB  
Article
Explainable AI for Oral Cancer Diagnosis: Multiclass Classification of Histopathology Images and Grad-CAM Visualization
by Jelena Štifanić, Daniel Štifanić, Nikola Anđelić and Zlatan Car
Biology 2025, 14(8), 909; https://doi.org/10.3390/biology14080909 - 22 Jul 2025
Viewed by 352
Abstract
Oral cancer is typically diagnosed through histological examination; however, the primary issue with this type of procedure is tumor heterogeneity, where a subjective aspect of the examination may have a direct effect on the treatment plan for a patient. To reduce inter- and [...] Read more.
Oral cancer is typically diagnosed through histological examination; however, the primary issue with this type of procedure is tumor heterogeneity, where a subjective aspect of the examination may have a direct effect on the treatment plan for a patient. To reduce inter- and intra-observer variability, artificial intelligence algorithms are often used as computational aids in tumor classification and diagnosis. This research proposes a two-step approach for automatic multiclass grading using oral histopathology images (the first step) and Grad-CAM visualization (the second step) to assist clinicians in diagnosing oral squamous cell carcinoma. The Xception architecture achieved the highest classification values of 0.929 (±σ = 0.087) AUCmacro and 0.942 (±σ = 0.074) AUCmicro. Additionally, Grad-CAM provided visual explanations of the model’s predictions by highlighting the precise areas of histopathology images that influenced the model’s decision. These results emphasize the potential of integrated AI algorithms in medical diagnostics, offering a more precise, dependable, and effective method for disease analysis. Full article
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22 pages, 4100 KiB  
Article
Investigation of the CTLA-4–CD28 Axis in Oral Squamous Cell Carcinoma
by Ferdinand Feldmeier, Manuel Weber, Franca Pacelli, Christoph Vogl, Jacek Glajzer, Leah Trumet, Mayte Buchbender, Carol Geppert, Marco Kesting and Jutta Ries
J. Clin. Med. 2025, 14(14), 5171; https://doi.org/10.3390/jcm14145171 - 21 Jul 2025
Viewed by 504
Abstract
Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with low survival rates, especially in advanced stages, despite improved therapies. New developments show that immune checkpoint inhibitors (ICIs) are promising treatment options. A better understanding of immune suppression in OSCC could enable new therapeutic approaches and effective ICI combinations. Methods: The aim of this cross-sectional study was to investigate the significance of the differential expression of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), CD28 and their ligands CD80 and CD86 for the diagnosis and treatment of OSCC. To this end, mRNA expression was analysed by RT-PCR and compared in 65 healthy oral mucosa samples (NOM) and 104 OSCC samples. Results: The expression of CTLA-4 (a soluble and membrane-bound isoform) was increased in OSCC by 1.72-fold (p = 0.004) and 6.88-fold (p < 0.001), respectively. There was no significant difference for CD28 (p = 0.283), nor for the soluble isoform of CD86 (p = 0.845). The membrane isoform of CD86 was increased in OSCC by a factor of 1.39 (p = 0.009) and CD80 by 6.11-fold (p < 0.001). Conclusions: The results show a significant association between CTLA-4, CD80 and membrane-bound CD86 expression and diagnosis. They could improve diagnostics in multi-marker approaches and serve as therapeutic targets for ICI strategies. In particular, the data indicate a stronger immunosuppressive role of CD80 compared to CD86 in a tumor tissue context, suggesting the exploration of anti-CTLA-4 and anti-CD80 antibody combinations in animal models. Full article
(This article belongs to the Special Issue Oral Cancer: Clinical Updates and Perspectives)
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16 pages, 2201 KiB  
Article
Oral Squamous Cell Carcinoma Exosomes Upregulate PIK3/AKT, PTEN, and NOTCH Signaling Pathways in Normal Fibroblasts
by Dijana Mitic, Milica Jaksic Karisik, Milos Lazarevic, Jelena Carkic, Emilia Zivkovic, Olivera Mitrovic Ajtic and Jelena Milasin
Curr. Issues Mol. Biol. 2025, 47(7), 568; https://doi.org/10.3390/cimb47070568 - 19 Jul 2025
Viewed by 351
Abstract
Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. [...] Read more.
Exosomes, small extracellular vesicles secreted by various cell types, have gained significant attention in cancer investigations. Isolation and characterization of exosomes derived from DOK (dysplastic oral keratinocyte), SCC (squamous cell carcinoma) and HaCaT (normal skin keratinocyte) cell lines and microRNA profiling were conducted. Magnetic sorting was applied to obtain pure exosomes. Morphology and size were characterized by transmission electron microscopy and nanoparticle tracking analysis. Validation of membrane exosomal markers (CD9, CD63) was performed via Western blotting. MiR-21, miR-31, and miR-133 levels were analyzed in exosomes and parent cells by qPCR. Biological effects of the exosomes were tested by adding them to fibroblast cultures and determining the expression of relevant carcinogenesis markers by qPCR. Exosomes appeared as cup-shaped nano-sized particles, and there was no difference regarding particle diameter and concentration between the three types of exosomes. The oncogenic miR-21 was significantly upregulated both in SCC and SCC-derived exosomes compared to DOK and HaCaT cells and their respective exosomes. However, miR-31 unexpectedly showed the highest expression in normal cells and the lowest in HaCaT exosomes. MiR-133, the tumor suppressor miRNA, was downregulated in both SCC and DOK cells compared to normal (HaCaT) cells, while the opposite situation was observed in exosomes, with HaCaT cells showing the lowest levels of miR-133. The differences in exosome content were reflected in signaling pathway activation in exosome-treated fibroblasts, with SCC exosomes exerting the most potent effect on several cancer-related pathways, notably PIK3/AKT, PTEN, and NOTCH signaling cascades. Full article
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26 pages, 19818 KiB  
Article
Evodiamine Boosts AR Expression to Trigger Senescence and Halt Proliferation in OSCC Cells
by Gang Chen, Hong-Liang Du, Jia-Nan Liu, Jie Cheng, Jing Chen, Xiao-Yang Yin, Hu-Lai Wei and Jing Wang
Curr. Issues Mol. Biol. 2025, 47(7), 558; https://doi.org/10.3390/cimb47070558 - 17 Jul 2025
Viewed by 384
Abstract
Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant [...] Read more.
Oral squamous cell carcinoma (OSCC), an aggressive and poorly prognosed subtype of head and neck squamous cell carcinoma (HNSCC), has prompted urgent calls for innovative therapeutic approaches. Evodiamine (EVO), a natural alkaloid extracted from the Chinese herb Evodia rutaecarpa, has demonstrated significant potential in curbing tumor cell proliferation and slowing tumor expansion. However, its specific effects on cell senescence within the context of OSCC have remained shrouded in uncertainty. This study delves into the mechanisms of EVO’s impact on OSCC by harnessing databases such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and CellAge to pinpoint potential targets and carry out in-depth bioinformatics analysis. The findings reveal that EVO can markedly enhance the expression of the androgen receptor (AR) in OSCC cells, inducing cellular senescence and thereby inhibiting tumor progression. Furthermore, the research indicates that AR expression is considerably lower in OSCC tissues than in normal tissues. This low expression of AR in tumor tissues is closely associated with advanced clinical stages and unfavorable prognoses in HNSCC patients. These discoveries open up new avenues for therapeutic strategies, and suggest that AR holds promise as a potential therapeutic target for OSCC, and EVO may amplify its antitumor effects by enhancing AR-mediated cellular senescence in the treatment of OSCC. Full article
(This article belongs to the Section Molecular Medicine)
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12 pages, 2258 KiB  
Article
In Vitro Efficacy of Water-Soluble Mercaptopyridine-Substituted Oxotitanium (IV) Phthalocyanine Compounds in Photodynamic Therapy of Oral Squamous Cell Carcinoma
by Merve Çiftçi, Mansur Doğan, Didem Duman, Özge Göktuğ Temiz, Mahmut Durmuş and Efkan Bağda
Medicina 2025, 61(7), 1285; https://doi.org/10.3390/medicina61071285 - 17 Jul 2025
Viewed by 225
Abstract
Background and Objectives: The efficacy of newly synthesized water-soluble octa-mercaptopyridine-substituted oxotitanium (IV) phthalocyanine (oxo-TiPc) and copper (II) phthalocyanine (CuPc) compounds in photodynamic therapy (PDT) was investigated using human tongue squamous cell cancer cell line (SCC-9, ATCC) cultures. Materials and Methods: A [...] Read more.
Background and Objectives: The efficacy of newly synthesized water-soluble octa-mercaptopyridine-substituted oxotitanium (IV) phthalocyanine (oxo-TiPc) and copper (II) phthalocyanine (CuPc) compounds in photodynamic therapy (PDT) was investigated using human tongue squamous cell cancer cell line (SCC-9, ATCC) cultures. Materials and Methods: A laser light source with a wavelength of 635 nm was used for this study. The cytotoxic values of the cancerous (SCC-9) and healthy (L-929) cell samples to which different Pc concentrations were applied under laser light were evaluated spectroscopically with the XTT method. Results: The oxo-TiPc compound exhibited a significantly lower IC50 value (46.8 µM) for SCC-9 cells compared to the CuPc compound (286.2 µM), indicating higher anticancer activity. This cytotoxicity may be due to decreased aggregation and enhanced reactive oxygen species (ROS) formation. Double-staining tests confirmed that oxo-TiPc-induced cell death included both apoptosis and necrosis. Conclusions: The findings show that the oxo-TiPc compound, unlike the CuPc compound, exhibited more selective toxicity to the SCC-9 cell line and has a higher phototoxic effect. Full article
(This article belongs to the Section Pharmacology)
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13 pages, 6081 KiB  
Article
TrkA Expression as a Novel Prognostic Biomarker in Oral Squamous Cell Carcinoma
by Aleksandra Ciarka, Filip Skowronek, Przemysław Miłosz, Michał Kunc, Robert Burdach, Monika Sakowicz-Burkiewicz, Barbara Jereczek-Fossa, Anna Starzyńska and Rafał Pęksa
Int. J. Mol. Sci. 2025, 26(14), 6847; https://doi.org/10.3390/ijms26146847 - 16 Jul 2025
Viewed by 270
Abstract
Oral squamous cell carcinoma (OSCC) remains a significant global health challenge, representing 90% of oral malignancies. Despite therapeutic advances, patient outcomes remain poor, highlighting the need for novel prognostic biomarkers and treatment targets. We investigated the expression patterns of NTRK genes and their [...] Read more.
Oral squamous cell carcinoma (OSCC) remains a significant global health challenge, representing 90% of oral malignancies. Despite therapeutic advances, patient outcomes remain poor, highlighting the need for novel prognostic biomarkers and treatment targets. We investigated the expression patterns of NTRK genes and their corresponding proteins (TrkA, TrkB, and TrkC) in OSCC, analyzing their relationships with clinical outcomes and potential as therapeutic targets. We examined 93 OSCC tissue samples using immunohistochemistry and quantitative real-time PCR. Protein expression was quantified using the H-score method. We analyzed correlations between Trk expression, clinicopathological parameters, and 2-year survival rates using chi-square tests, Mann–Whitney U tests, and Kaplan–Meier survival analysis. TrkA showed near-universal expression (97.8%—91 patients) in OSCC samples, with high expression levels significantly correlating with lower tumor grade (p = 0.014) and improved 2-year survival (p = 0.011). While TrkB and TrkC were expressed in 65.5% and 84.9% of cases, respectively, neither showed significant associations with clinical parameters. NTRK2 and NTRK3 mRNA levels demonstrated a strong positive correlation (R = 0.64, p = 0.002), suggesting coordinated regulation. Our findings establish TrkA as a promising positive prognostic marker in OSCC, warranting investigation as a therapeutic target. The strong correlation between NTRK2 and NTRK3 expression suggests shared regulatory mechanisms in OSCC pathogenesis. Further studies with larger cohorts and longer follow-up periods are needed to validate these findings and explore their therapeutic implications. Full article
(This article belongs to the Special Issue Biology of Oral Cancer)
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26 pages, 1644 KiB  
Review
Therapeutic Targeting of Apoptosis, Autophagic Cell Death, Necroptosis, Pyroptosis, and Ferroptosis Pathways in Oral Squamous Cell Carcinoma: Molecular Mechanisms and Potential Strategies
by Po-Chih Hsu, Chung-Che Tsai, Ya-Hsuan Lin and Chan-Yen Kuo
Biomedicines 2025, 13(7), 1745; https://doi.org/10.3390/biomedicines13071745 - 16 Jul 2025
Viewed by 481
Abstract
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor prognosis, largely due to its high metastatic potential and resistance to conventional therapies. Recent advances in cancer biology have underscored the significance of regulated cell death pathways, including apoptosis, autophagic [...] Read more.
Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with poor prognosis, largely due to its high metastatic potential and resistance to conventional therapies. Recent advances in cancer biology have underscored the significance of regulated cell death pathways, including apoptosis, autophagic cell death (ACD), necroptosis, pyroptosis, and ferroptosis, in modulating tumor progression and therapeutic responses. This review provides the current insights into the molecular mechanisms underlying these cell death pathways and explores their therapeutic relevance in OSCC. Restoration of apoptosis using BH3 mimetics, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonists, and p53 reactivators shows promise for sensitizing OSCC cells to treatment. Autophagy plays context-dependent roles in cancer, acting as a tumor suppressor during early carcinogenesis by maintaining cellular homeostasis, and as a tumor promoter in established tumors by supporting cancer cell survival under stress. Targeting necroptosis and pyroptosis has emerged as a novel strategy for inducing cancer cell death, with compounds such as acetylshikonin and okanin demonstrating antitumor effects. Additionally, the induction of ferroptosis via lipid peroxidation and glutathione peroxidase 4 (GPX4) inhibition offers a promising avenue for overcoming drug resistance, with agents such as quercetin and trifluoperazine exhibiting preclinical success. Integration of these therapeutic approaches may enhance the OSCC treatment efficacy, reduce chemoresistance, and provide novel prognostic biomarkers for clinical management. Future studies should focus on optimizing combinatorial strategies that effectively leverage these pathways to improve OSCC patient outcomes. Full article
(This article belongs to the Special Issue Oral Cancer: From Pathophysiology to Novel Therapeutic Approach)
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21 pages, 2238 KiB  
Review
Cell-Free DNA as a Prognostic Biomarker in Oral Carcinogenesis and Oral Squamous Cell Carcinoma: A Translational Perspective
by Pietro Rigotti, Alessandro Polizzi, Vincenzo Quinzi, Andrea Blasi, Teresa Lombardi, Eleonora Lo Muzio and Gaetano Isola
Cancers 2025, 17(14), 2366; https://doi.org/10.3390/cancers17142366 - 16 Jul 2025
Viewed by 432
Abstract
Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic [...] Read more.
Oral squamous cell carcinoma (OSCC) remains one of the most common malignancies in the head and neck region, often preceded by a spectrum of oral potentially malignant disorders (OPMDs). Despite advances in diagnostic methods, reliable and non-invasive biomarkers for early detection and prognostic stratification are still lacking. In recent years, circulating cell-free DNA (cfDNA) has emerged as a promising liquid biopsy tool in several solid tumors, offering insights into tumor burden, heterogeneity, and molecular dynamics. However, its application in oral oncology remains underexplored. This study aims to review and discuss the current evidence on cfDNA quantification and mutation analysis (including TP53, NOTCH1, and EGFR) in patients with OPMDs and OSCC. Particular attention is given to cfDNA fragmentation patterns, methylation signatures, and tumor-specific mutations as prognostic and predictive biomarkers. Moreover, we highlight the challenges in standardizing pre-analytical and analytical workflows in oral cancer patients and explore the potential role of cfDNA in monitoring oral carcinogenesis. Understanding cfDNA dynamics in the oral cavity might offer a novel, minimally invasive strategy to improve early diagnosis, risk assessment, and treatment decision-making in oral oncology. Full article
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