Therapeutic Resistance in Oral Cancer: Mechanisms, Biomarkers, and Novel Strategies to Restore Treatment Responses

Dear Colleagues,

Oral squamous cell carcinoma (OSCC), the most prevalent malignancy of the oral cavity, continues to present significant clinical challenges due to its frequent resistance to standard-of-care treatments such as chemotherapy, radiotherapy, and immunotherapy. Despite advances in molecular diagnostics and treatment modalities, therapeutic resistance remains a major barrier in achieving durable responses and improved survival in OSCC patients.

Resistance to therapy is a multifaceted process driven by tumor-intrinsic alterations (e.g., genetic mutations, epigenetic changes, and metabolic reprogramming) and tumor-extrinsic factors (e.g., immunosuppressive tumor microenvironments and stromal remodeling). The emergence of resistant subclones, impaired drug delivery, and immunotherapy evasion mechanisms further exacerbates disease progression and recurrence.

To address this pressing issue, there is a growing need to achieve the following:

• Decipher the molecular and cellular mechanisms underlying therapeutic resistance;
• Identify robust predictive biomarkers to stratify responders from non-responders; and
• Develop novel therapeutic agents or combination strategies to overcome resistance and restore treatment sensitivity.

For this Special Issue of Biomedicines, entitled “Therapeutic Resistance in Oral Cancer: Mechanisms, Biomarkers, and Novel Strategies to Restore Treatment Responses”, we welcome submissions that explore the following:

• Mechanistic insights into chemoresistance, radioresistance, or immunotherapy resistance in OSCC;
• Novel biomarkers predictive of treatment responses or resistance;
• Preclinical and clinical studies on drug repurposing or novel agents targeting resistant OSCC;
• Combination strategies designed to enhance responses to standard-of-care therapies;
• Tumor microenvironment and immune landscape alterations contributing to resistance;
• Systems biology and omics-based approaches to predicting or monitoring treatment outcomes.

Original research articles, reviews, systematic reviews, and meta-analyses are all welcome. Submissions focusing on translational aspects and therapeutic innovations in OSCC and HNSCC are especially encouraged.

We look forward to receiving your valuable contributions to advance our understanding and treatment of therapeutic resistance in oral cancer.

Dr. Vui King Vincent-Chong
Guest Editor

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• oral cancer
• OSCC
• chemotherapy
• radiotherapy
• immunotherapy
• therapeutic resistance
• HNSCC
• biomarker
• tumor microenvironment