Abstract
Head and Neck cancer survival has continued to remain around 50% despite treatment advances. It is thought that cancer stem cells play a key role in promoting tumor heterogeneity, treatment resistance, metastasis, and recurrence in solid malignancies including head and neck cancer. Initial studies identified cancer stem cell markers including CD44 and ALDH in head and neck malignancies and found that these cells show aggressive features in both in vitro and in vivo studies. Recent evidence has now revealed a key role of the tumor microenvironment in maintaining a cancer stem cell niche and promoting cancer stem cell plasticity. There is an increasing focus on identifying and targeting the crosstalk between cancer stem cells and surrounding cells within the tumor microenvironment (TME) as new therapeutic potential, however understanding how CSC maintain a stem-like state is critical to understanding how to therapeutically alter their function. Here we review the current evidence for cancer stem cell plasticity and discuss how interactions with the TME promote the cancer stem cell niche, increase tumor heterogeneity, and play a role in treatment resistance.
Highlights
Head and neck cancer accounts for approximately 60,000 new cancer diagnoses and 13,000 cancer related deaths in the United States each year
Whether the conversion between Cancer stem cells (CSCs) and non-stem can cells is driven by environmental factors, genetic alteration, or a stochastic process is still debated (Morel et al, 2008; Medema 2013) these results suggests that targeting the mediating factors that control the interconversion and maintenance of the CSC niche offers a potential therapeutic option
Cancer stem cells residing within hypoxic niches contribute to the overall resistance of head and neck cancer (HNC) to radiation therapy and additional evidence suggests this may be mediated through a Hif-1 alpha mediated mechanism (Wozny et al, 2017)
Summary
Head and neck cancer accounts for approximately 60,000 new cancer diagnoses and 13,000 cancer related deaths in the United States each year. Proponents of the cancer stem cell model argue that because CSCs are thought to be relatively resistant to radiation and chemotherapy; they evade initial treatment modalities and subsequently are able to recreate the heterogeneous tumor. It is CD44’s role as a surface protein involved in cellcell interactions, adhesion, and migration that further supports the mechanistic study of CD44+ stem cells in interaction with the tumor microenvironment (Škerlová et al, 2015; Ferreira et al, 2018; Choi et al, 2021) These data support the clinical importance of CSCs in tumorigenesis, metastasis, and treatment failure. We discuss the plasticity of cancer stem cells and impact of the TME, metabolic reprogramming, and potential translational strategies to target head and neck CSCs plasticity as a means for novel therapeutic strategies
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