Research Topic

The Role of Cancer Stem Cells in Oral Cancer Progression and Therapeutic Resistance

About this Research Topic

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and forms heterogeneous tumors consisting of a mixture of epithelial cells displaying different degrees of cellular differentiation, metastatic potential and response to cancer treatment. Such heterogeneity is partially explained by the cancer stem cell (CSC) model, proposed nearly a half century ago. In this model, the cancer growth is sustained by a CSC subpopulation which forms a small fraction of the total tumor cells. CSCs are able both to self-renew and to generate transient amplifying cells that have a limited expansion capability to form non-proliferative terminally differentiating cells. CSCs were initially identified in hematological malignancies but have since been found in many solid tumors, including oral cancer. Typically, their identification is based on surface marker expression, activity of ALDH1, and their tumorigenic capacity when injected in immunocompromised mice. It has been shown that CSC play a role in tumor initiation, metastasis, immune evasion and therapeutic resistance. Recently, it was found that tumor cells can detach from the primary or metastatic sites to circulate in the blood where they can be identified by their expression of CSC markers.

In oral cancer, CSCs have been shown to form a heterogeneous cellular population that switches dynamically between epithelial and mesenchymal phenotypes. During such epithelial to mesenchymal transition (EMT) they acquire traits that favor cellular migration, invasion, metastasis, and treatment resistance. Oral CSC are highly resistant to chemo- and radio-therapies, and are increased in numbers following such treatments. The expression of CSC markers has been found to impact negatively in overall survival and prognosis. Characterization of the CSC population is thus fundamental to an understanding of the role of CSCs in the context of head and neck cancer. Ultimately, stem cell identification is expected to provide prognostic abilities and therapeutic targeting of the CSC population to enhance the efficacy of oral cancer therapy.

The Editors of this Research Topic are interested in receiving original research articles, reviews and mini reviews involving CSCs in all types of oral malignancies that cover the following areas:
• Head and Neck CSC identification, characteristics and molecular signatures;
• The Head and Neck CSC niche and its relationship to the tumor microenvironment;
• Mechanisms to circumvent the chemo- and radio-therapy resistance acquired by CSC in Head and Neck cancer;
• Roles of immunotherapy as an adjuvant therapy to eradicate the Head and neck CSC;
• The genes and proteins involved in signaling pathways associated with CSC properties;
• The CSC phenotype and properties of circulating tumor cells.


Keywords: Oral Cancer, OSCC, cancer stem cell, EMT, therapy resistance


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.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and forms heterogeneous tumors consisting of a mixture of epithelial cells displaying different degrees of cellular differentiation, metastatic potential and response to cancer treatment. Such heterogeneity is partially explained by the cancer stem cell (CSC) model, proposed nearly a half century ago. In this model, the cancer growth is sustained by a CSC subpopulation which forms a small fraction of the total tumor cells. CSCs are able both to self-renew and to generate transient amplifying cells that have a limited expansion capability to form non-proliferative terminally differentiating cells. CSCs were initially identified in hematological malignancies but have since been found in many solid tumors, including oral cancer. Typically, their identification is based on surface marker expression, activity of ALDH1, and their tumorigenic capacity when injected in immunocompromised mice. It has been shown that CSC play a role in tumor initiation, metastasis, immune evasion and therapeutic resistance. Recently, it was found that tumor cells can detach from the primary or metastatic sites to circulate in the blood where they can be identified by their expression of CSC markers.

In oral cancer, CSCs have been shown to form a heterogeneous cellular population that switches dynamically between epithelial and mesenchymal phenotypes. During such epithelial to mesenchymal transition (EMT) they acquire traits that favor cellular migration, invasion, metastasis, and treatment resistance. Oral CSC are highly resistant to chemo- and radio-therapies, and are increased in numbers following such treatments. The expression of CSC markers has been found to impact negatively in overall survival and prognosis. Characterization of the CSC population is thus fundamental to an understanding of the role of CSCs in the context of head and neck cancer. Ultimately, stem cell identification is expected to provide prognostic abilities and therapeutic targeting of the CSC population to enhance the efficacy of oral cancer therapy.

The Editors of this Research Topic are interested in receiving original research articles, reviews and mini reviews involving CSCs in all types of oral malignancies that cover the following areas:
• Head and Neck CSC identification, characteristics and molecular signatures;
• The Head and Neck CSC niche and its relationship to the tumor microenvironment;
• Mechanisms to circumvent the chemo- and radio-therapy resistance acquired by CSC in Head and Neck cancer;
• Roles of immunotherapy as an adjuvant therapy to eradicate the Head and neck CSC;
• The genes and proteins involved in signaling pathways associated with CSC properties;
• The CSC phenotype and properties of circulating tumor cells.


Keywords: Oral Cancer, OSCC, cancer stem cell, EMT, therapy resistance


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.

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Submission Deadlines

28 July 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

28 July 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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