Abstract
Head and neck squamous cell carcinoma (HNSCC) is currently one of the 10 most common malignancies worldwide, characterized by a biologically highly diverse group of tumors with non-specific biomarkers and poor prognosis. The incidence rate of HNSCC varies widely throughout the world, with an evident prevalence in developing countries such as those in Southeast Asia and Southern Africa. Tumor relapse and metastasis following traditional treatment remain major clinical problems in oral cancer management. Current evidence suggests that therapeutic resistance and metastasis of cancer are mainly driven by a unique subpopulation of tumor cells, termed cancer stem cells (CSCs), or cancer-initiating cells (CICs), which are characterized by their capacity for self-renewal, maintenance of stemness and increased tumorigenicity. Thus, more understanding of the molecular mechanisms of CSCs and their behavior may help in developing effective therapeutic interventions that inhibit tumor growth and progression. This review provides an overview of the main signaling cascades in CSCs that drive tumor repropagation and metastasis in oral cancer, with a focus on squamous cell carcinoma. Other oral non-SCC tumors, including melanoma and malignant salivary gland tumors, will also be considered. In addition, this review discusses some of the CSC-targeted therapeutic strategies that have been employed to combat disease progression, and the challenges of targeting CSCs, with the aim of improving the clinical outcomes for patients with oral malignancies. Targeting of CSCs in head and neck cancer (HNC) represents a promising approach to improve disease outcome. Some CSC-targeted therapies have already been proven to be successful in pre-clinical studies and they are now being tested in clinical trials, mainly in combination with conventional treatment regimens. However, some studies revealed that CSCs may not be the only players that control disease relapse and progression of HNC. Further, clinical research studying a combination of therapies targeted against head and neck CSCs may provide significant advances.
Highlights
Head and neck cancer is a heterogenous group of tumors which mainly arise in the oral cavity, oropharynx, hypopharynx, salivary glands, paranasal sinuses and larynx [1]
Multiple other ligands, including transforming growth factor-α (TGF-α), can activate epidermal growth factor receptor (EGFR); overexpression of such ligands could be implicated in adenoid cystic carcinoma (ACC) pathogenesis [145]. These results suggest that EGFR may utilize multiple mechanisms to promote cancer stem cells (CSCs) self-renewal and stemness in ACC (Table 1)
Consistent with this study, another clinical trial observed a response with lapatinib treatment with prolonged tumor stabilization of more than 6 months in recurrent or metastatic salivary gland carcinoma patients, suggesting that targeted therapy with anti-EGFR therapeutics may improve the clinical outcomes of patients suffering from malignant salivary gland tumors [199]
Summary
Head and neck cancer is a heterogenous group of tumors which mainly arise in the oral cavity, oropharynx, hypopharynx, salivary glands, paranasal sinuses and larynx [1]. Previous studies reported a role for CD10 in the differentiation and growth of neoplastic cells and that its expression was associated with tumor size, histological grade of malignancy, local recurrence, and therapeutic resistance in HNSCC [36, 37].
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