Head and neck cancer management and cancer stem cells implication

Abstract

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal linings of the upper aerodigestive tract and are heterogeneous in nature. Risk factors for HNSCCs are smoking, excessive alcohol consumption, and the human papilloma virus. Conventional treatments are surgery, radiotherapy, chemotherapy, or a combined modality; however, no international standard mode of therapy exists. In contrast to the conventional model of clonal evolution in tumor development, there is a newly proposed theory based on the activity of cancer stem cells (CSCs) as the model for carcinogenesis. This "CSC hypothesis" may explain the high mortality rate, low response to treatments, and tendency to develop multiple tumors for HNSCC patients. We review current knowledge on HNSCC etiology and treatment, with a focus on CSCs, including their origins, identifications, and effects on therapeutic options.

Keywords: ABC, ATP-binding cassette transporters; ATC, amplifying transitory cell; Antineoplastic agents; BMI-1, B cell-specific Moloney murine leukemia virus integration site 1; Cancer stem cells; Cancer treatment; Carcinoma; EGFR, epidermal growth factor receptor; HIFs, hypoxia-inducible factors; Head and neck cancer; MDR1, Multidrug Resistance Protein 1; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; Squamous cell; TKIs, tyrosine kinase inhibitors.

Fig. 1

Models of tumor heterogeneity. Tumors are formed from cells that are heterogenous phenotypically and functionally. There are 2 most acceptable theories as to how this heterogeneity occur. According to the stochastic model, all tumor cells are biologically equal, however, intrinsic and extrinsic factors affect their behavior causing this variability. This means tumor-initiating activity cannot be enriched by isolating cells based on intrinsic features. In contrast, the hierarchy model (Cancer stem cell model) hypothesize the existence of biologically different classes of cells each has its own function and behavior. Only a subset of cells can start the tumorgenicity; these cancer stem cells possess two main criteria, self-renewal and multilineage differentiation, giving them the ability to form the bulk of the tumor. This model speculate that tumor-initiating cells can be identified and sorted based on intrinsic characteristics.

Fig. 2

Hypothesis suggesting origin of cancer stem cells. In the process of normal differentiation, a cell differentiates to form two cells, differentiated and primitive. A terminally differentiated cell is formed from precursor progenitor cell and finally undergoes apoptosis. CSC may originate from a normal stem cell (Hypothesis number 1), a normal progenitor cell (Hypothesis number 2), or a normal differentiated cell (Hypothesis number 3) by genetic mutation which will activate self-renewal genes. This figure and figure legend were originally published in (Shah et al., 2014) under a Creative Commons license.

Fig. 3

Therapeutic targeting strategies for CSCs. The traditional cancer therapies kill differentiated cancer cells but fail to target CSCs, resulting in cancer relapse. However, CSC-targeted therapies can eliminate or differentiate the CSCs, and the remaining and resulting differentiated cancer cells will die thereafter. But it is promising to combine CSC-targeted therapies and traditional therapies for depleting CSCs as well as killing differentiated cancer cells, this combination therapy may have the benefits of increased efficacy and quick action. This figure and figure legend were originally published in (Han et al., 2013) under a Creative Commons license.