Oral Squamous Cell Carcinoma: From Pathogenesis to Targeted Therapy
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".
Deadline for manuscript submissions: 31 March 2026 | Viewed by 42
Special Issue Editors
Interests: OSCC; HPV; oral potentially malignant lesions; MRONJ; oral microbiome
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Oral squamous cell carcinoma (OSCC) represents the most common malignancy of the oral cavity and a major subset of head and neck cancers. Globally, OSCC accounts for approximately 650,000 new cases and nearly 300,000 deaths each year, with a 5-year survival rate at around 50%, without improvements despite advances in prevention campaigns and treatment modalities. The high mortality and morbidity burden is largely attributable to late-stage diagnosis, frequent locoregional recurrences, and the development of resistance to conventional treatments, which lead to significant challenges in OSCC management and control.
Recent research has begun to unravel the genetic alterations, signaling pathways, and microenvironmental changes driving OSCC initiation and progression, alongside emerging evidence of immune evasion and tumor-promoting inflammation. This includes the complex interplay of genetic, epigenetic, and environmental factors. Key alterations include TP53 mutations, EGFR overexpression, and p16 hypermethylation. Lifestyle and environmental risk factors, such as tobacco, alcohol, betel quid chewing, nutritional deficiencies, and HPV infection (especially in specific subsites), are well recognized. However, scarce information is available on OSCC in young patients without classical risk factors or OPMD precursors.
OSCC exhibits marked cellular heterogeneity and is strongly influenced by its tumor microenvironment. Crosstalk with cancer-associated fibroblasts, immune cells, and extracellular matrix components contributes to invasion, immune evasion, and therapeutic resistance. Both intrinsic and acquired resistance mechanisms remain a critical obstacle to treatment success. At present, EGFR inhibitors (cetuximab) are the only approved targeted therapy for OSCC, while anti-VEGF agents (i.e., bevacizumab) are under investigation. Immunotherapy, particularly PD-1/PD-L1 checkpoint inhibitors (pembrolizumab, nivolumab), has significantly changed the therapeutic landscape, demonstrating efficacy in recurrent/metastatic disease and, more recently, in perioperative settings. Novel therapeutic strategies, including molecular combinations (i.e., HDAC inhibitors with metformin, MEK inhibitors such as trametinib, and cold atmospheric plasma), are rapidly emerging.
Advances in genomic profiling and single-cell sequencing now enable refined biomarker discovery and precision diagnostics. Optimal OSCC management increasingly requires a multidisciplinary approach, integrating oncologists, surgeons, radiotherapists, pathologists, and molecular scientists to translate molecular insights into clinical benefit.
This Special Issue will provide a comprehensive overview of recent advances in the understanding of oral squamous cell carcinoma, spanning its pathogenesis, early detection, and clinical management. By integrating research on oral potentially malignant disorders, molecular and immune biomarkers, and novel therapeutic approaches, this Special Issue will bridge basic science with translational and clinical perspectives.
We invite you to contribute to this Special Issue of the International Journal of Molecular Sciences. Both original research articles and reviews are welcome.
Prof. Dr. Giuseppina Campisi
Dr. Vito Carlo Alberto Caponio
Guest Editors
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Keywords
- oral cancer
- oral potentially malignant disorders
- omics
- oral squamous cell carcinoma
- leukoplakia
- biomarkers
- tumor microenvironment
- immunotherapy
- target therapy
- HPV
- multidisciplinary team
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