Cancer Stem Cells in Oral Carcinogenesis: From Biomarkers to Therapeutic Innovation

Oral cancer research has recently focused on the intricate biology of cancer stem cells (CSCs), which are known to be key drivers of tumor initiation, progression, and recurrence in oral squamous cell carcinoma (OSCC). Despite advances in surgical and pharmacological treatments, the persistence of poor clinical outcomes is largely attributed to tumor heterogeneity and the adaptive nature of CSCs. Current literature establishes that CSCs possess both self-renewal and differentiation capabilities, contributing to metastasis, chemotherapy resistance, immune evasion, and ultimately, disease relapse. While new studies are unraveling molecular pathways and identifying specific surface markers linked to CSCs, our understanding of their clinical relevance remains incomplete. Conventional therapies often fail to eradicate CSCs, underscoring the urgent need for better diagnostic tools and innovative treatment strategies. Recent investigations have spotlighted novel biomarkers, elucidated regulatory signaling axes, and developed experimental models to further probe CSC-driven cellular processes. However, significant knowledge gaps persist in reliably identifying CSC populations, clarifying their molecular crosstalk, and translating experimental findings into personalized therapies. Addressing these issues is essential to overcoming therapeutic resistance and improving patient prognosis.

This Research Topic aims to consolidate current knowledge and foster new advances in the biology, clinical significance, and therapeutic targeting of cancer stem cells in oral carcinogenesis. We seek to address unresolved questions surrounding the molecular mechanisms and signaling pathways supporting CSC survival, tumor aggressiveness, and resistance to conventional treatments. By promoting the exploration of emerging diagnostic and prognostic biomarkers, as well as novel therapeutic modalities, this topic aspires to accelerate translational and clinical progress in targeting CSCs. Ultimately, the objective is to deepen our mechanistic understanding and create a rational framework for personalized therapies that mitigate relapse and improve long-term outcomes in OSCC patients.

The Research Topic welcomes original and review articles that broaden the scope of mechanistic, translational, and preclinical research dedicated to CSCs in oral carcinogenesis. Contributions should be focused on OSCC and associated premalignant oral disorders, but may also encompass broader mechanistic insights with translational relevance. Specific themes include, but are not limited to:
• Identification and characterization of CSC populations and tumor heterogeneity
• Discovery and validation of diagnostic and prognostic CSC biomarkers
• Elucidation of regulatory signaling pathways (e.g., Notch, Wnt, Hedgehog, BMI-1, ALDH1) supporting CSC functions
• CSC-mediated intercellular communication, including roles of miRNAs and long non-coding RNAs
• Mechanisms underpinning chemoresistance and radiotherapy resistance mediated by CSCs
• Innovative therapeutic approaches targeting CSCs, including small molecules, immunotherapies, phytochemicals, and nucleic acid-based interventions
• Translational studies incorporating in vivo models, 3D organoids, and comprehensive omics approaches

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Community Case Study
• Curriculum, Instruction, and Pedagogy
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Oral Carcinogenesis, Oral Cancer Stem Cells (OCSCs), Biomarkers, Drug Resistance, Therapeutic Targets

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.