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

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 June 2026 | Viewed by 697

Special Issue Editor

Special Issue Information

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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Keywords

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

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Published Papers (1 paper)

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Review

15 pages, 622 KB  
Review
Target Discovery in Head-and-Neck Squamous Cell Carcinoma: Genome-Wide CRISPR Screens Illuminate Therapeutic Resistance and Actionable Dependencies
by Vui King Vincent-Chong
Biomedicines 2025, 13(12), 3012; https://doi.org/10.3390/biomedicines13123012 - 8 Dec 2025
Viewed by 416
Abstract
Head-and-neck squamous cell carcinoma (HNSCC) remains a lethal malignancy with stagnant survival despite advances in surgery, radiotherapy, and systemic therapy. Beyond cetuximab and PD-1 inhibitors, there are only a few targeted options, which benefit only a minority of patients, underscoring the need for [...] Read more.
Head-and-neck squamous cell carcinoma (HNSCC) remains a lethal malignancy with stagnant survival despite advances in surgery, radiotherapy, and systemic therapy. Beyond cetuximab and PD-1 inhibitors, there are only a few targeted options, which benefit only a minority of patients, underscoring the need for new biomarkers and druggable dependencies. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) Cas9 screening now enables systematic, high-specificity investigation of gene function to reveal determinants of tumor proliferation, survival, and therapy response. Compared with RNA interference, CRISPR provides cleaner on-target knockout and more interpretable phenotypes, allowing efficient discovery of essential genes and synthetic-lethal interactions. Although the Cancer Dependency Map profiled 89 OSCC/HNSCC lines to nominate baseline dependencies, drug-perturbed states critical for understanding platinum resistance remain underexplored. Only a handful of HNSCC studies have applied genome-wide CRISPR cas9 screening: two mapped core essential genes; two mapped cisplatin resistance and radiation resistance; and others uncovered synthetic-lethal targets, including vulnerabilities to mTOR inhibition, EGFR inhibition, glutamine metabolism inhibition, and host determinants of oncolytic HSV-1 efficacy. This review synthesizes these findings, highlights methodological considerations (library design, coverage, and treatment duration), and integrates complementary functional data to prioritize targets for rational combinations. This review also provides information on the TCGA database and in vivo CRISPR screening that can accelerate precision therapeutics for patients with HNSCC. Full article
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