Cancer stem cells in head and neck squamous cell carcinoma: Treatment modalities

Abstract

Summary Head and neck squamous cell carcinoma (HNSCC) belongs to the most frequent cancer subtypes in the world. Mutations due to genetic and chromosomal instability, syndromes such as Fanconi anemia and the Bloom syndrome, environmental risk factors such as tobacco smoking, alcohol and human papillomavirus infection (HPV) subtypes 16,18,31,33,35,52,58 are implicated in its pathogenesis. The HNSCC belongs to the solid tumors of epithelial origin and consists of stromal, inflammatory, cancer cells and most importantly a fraction of them, the cancer stem cells (CSCs). The identification of the CSCs through their biomarkers such as CD44, CD10, CD166, CD133, CD271, ALDH, Oct4, Nanog, Sox2 and Bmi1, the maintenance of their subpopulation through epithelial to mesenchymal transition, the role of HPV infection regarding their prognosis and of their microenvironment regarding their resistance to therapy, all constitute key elements that must be taken thoroughly into consideration in order to develop an effective targeted therapy. There are already therapies in place targeting specific related biomarkers, important biochemical pathways and growth factors. The aim of this literature review is to illustrate the treatment modalities available against the cancer stem cells of head and neck squamous cell carcinoma.

Preliminary Study of the Cancer Stem Cells’ Biomarker CD147 in Leukoplakia: Dysplasia and Squamous Cell Carcinoma of Oral Epithelial Origin

“…They are responsible for the invasion and metastasis of cancer, as well as the development of chemotherapy and radiotherapy resistance. Targeting them successfully is therefore an important therapeutic goal and may be achieved by identifying specific biomarkers that are expressed by them [5]. The most frequently used CSC markers for head and neck squamous cell carcinoma are summarized in Table 5.…”

“…They are responsible for the phenomena of cancer invasion and metastasis, as well as the development of resistance to chemotherapy and radiotherapy. Targeting them successfully is therefore an important therapeutic goal and may be achieved by identifying specific antigens that are expressed by them [5]. Additionally, cancer stem cells are present both in potentially malignant lesions and in cancerous lesions, most probably intervening and mediating in the process of carcinogenesis [6].…”

The Role of Hedgehog Signaling Pathway in Head and Neck Squamous Cell Carcinoma

“…A few years later, CSC populations were also found in solid tumors [ 76 , 77 ]. Afterward, CSCs have been widely investigated and identified in various types of solid tumors, including HNC, but their role has not been fully described [ 6 , 7 , 76 , 78 ]. Several investigators showed that putative CSCs could be isolated from HNSCC tissue by their unique surface biomarker pattern expression [ 7 , 73 , 76 , 79 ].…”

“…Fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) were the first techniques used for CSC separation, which allow multi-biomarker sorting of stem cells at the same time with high purity and strong specificity [ 80 , 84 ]. Other methods used for CSC separation from tumors are based on cell culture with Hoechst 33342 or the colony-forming ability of CSCs [ 7 , 24 , 78 ]. So far, multiple markers, independently or in combination, have been documented by many authors as putative CSC markers in various tumors, including HNC [ 6 , 7 , 72 , 73 , 76 , 79 ].…”

“…So far, multiple markers, independently or in combination, have been documented by many authors as putative CSC markers in various tumors, including HNC [ 6 , 7 , 72 , 73 , 76 , 79 ]. These lists of putative CSC markers include specific biomolecules such as surface markers, drug transporters, enzymes, and components of several signaling pathways [ 7 , 72 , 73 , 76 , 78 , 81 ]. The majority of these biomarkers are cell surface and cytoplasmic proteins, sometimes located in nuclei.…”