Mechanisms involved in cancer stem cell resistance in head and neck squamous cell carcinoma

Abstract

Despite scientific advances in the Oncology field, cancer remains a leading cause of death worldwide. Molecular and cellular heterogeneity of head and neck squamous cell carcinoma (HNSCC) is a significant contributor to the unpredictability of the clinical response and failure in cancer treatment. Cancer stem cells (CSCs) are recognized as a subpopulation of tumor cells that can drive and maintain tumorigenesis and metastasis, leading to poor prognosis in different types of cancer. CSCs exhibit a high level of plasticity, quickly adapting to the tumor microenvironment changes, and are intrinsically resistant to current chemo and radiotherapies. The mechanisms of CSC-mediated therapy resistance are not fully understood. However, they include different strategies used by CSCs to overcome challenges imposed by treatment, such as activation of DNA repair system, anti-apoptotic mechanisms, acquisition of quiescent state and Epithelial-mesenchymal transition, increased drug efflux capacity, hypoxic environment, protection by the CSC niche, overexpression of stemness related genes, and immune surveillance. Complete elimination of CSCs seems to be the main target for achieving tumor control and improving overall survival for cancer patients. This review will focus on the multi-factorial mechanisms by which CSCs are resistant to radiotherapy and chemotherapy in HNSCC, supporting the use of possible strategies to overcome therapy failure.

New perspectives on biology, disease progression, and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

“…Even though not uncontroversially, cancer stem cells are considered as the source of cancer cell renewal and therapy resistance [24,87]. Some studies have therefore attempted to investigate HNSCC stem cells through single-cell transcriptomics.…”

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

“…The authors found that GLI mediates the expression of MGMT, which promotes resistance to TMZ [ 139 ]. There are results presenting that the HIF-1α/SHH/GLI1 axis is involved in the resistance of HNSCC to therapy and that HIF-1α reduces the response of HNSCC to radiotherapy [ 78 , 111 , 122 , 145 ]. There are several pieces of evidence documenting the association between CSCs and their signaling pathways and resistance to chemotherapy [ 109 , 113 , 145 ].…”

“…There are results presenting that the HIF-1α/SHH/GLI1 axis is involved in the resistance of HNSCC to therapy and that HIF-1α reduces the response of HNSCC to radiotherapy [ 78 , 111 , 122 , 145 ]. There are several pieces of evidence documenting the association between CSCs and their signaling pathways and resistance to chemotherapy [ 109 , 113 , 145 ]. Head and neck CSCs are able to avoid response to therapy due to their overexpression of ABC drug transporters and activation of several pathways [ 146 ].…”

Transcription Factors and Markers Related to Epithelial–Mesenchymal Transition and Their Role in Resistance to Therapies in Head and Neck Cancers

“…However, if the formation of distant metastasis occurs, it is also associated with a very poor prognosis [10][11][12]. Several pathways have been suggested to be involved in acquired and intrinsic resistance development, dissemination, and recurrence of HNSCC and have been recently reviewed in [2,13,14]. Here, we highlight the current knowledge of the process of epithelial-mesenchymal transition (EMT) in HNSCC.…”