Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers

Abstract

Purpose Resistance to chemotherapy and radiotherapy is the primary cause of a poor prognosis in oncological patients. Researchers identified many possible mechanisms involved in gaining a therapy-resistant phenotype by cancer cells, including alterations in intracellular drug accumulation, detoxification, and enhanced DNA damage repair. All these features are characteristic of stem cells, making them the major culprit of chemoresistance. This paper reviews the most recent evidence regarding the association between the stemness phenotype and chemoresistance in head and neck cancers. It also investigates the impact of pharmacologically targeting cancer stem cell populations in this subset of malignancies. Methods This narrative review was prepared based on the search of the PubMed database for relevant papers. Results Head and neck cancer cells belonging to the stem cell population are distinguished by the high expression of certain surface proteins (e.g., CD10, CD44, CD133), pluripotency-related transcription factors (SOX2, OCT4, NANOG), and increased activity of aldehyde dehydrogenase (ALDH). Chemotherapy itself increases the percentage of stem-like cells. Importantly, the intratumor heterogeneity of stem cell subpopulations reflects cell plasticity which has great importance for chemoresistance induction. Conclusions Evidence points to the advantage of combining classical chemotherapeutics with stemness modulators thanks to the joint targeting of the bulk of proliferating tumor cells and chemoresistant cancer stem cells, which could cause recurrence.

Top IHC/ISH Hacks for and Molecular Surrogates of Poorly Differentiated Sinonasal Small Round Cell Tumors

“…Sox2 expression and gene amplification have been identified as common events in the head and neck [ 21 , 22 ]; in the sinonasal region, amplification and/or overexpression of Sox2 has been demonstrated in squamous carcinoma (SNSCC), sinonasal undifferentiated carcinoma (SNUC), adenoid cystic carcinoma (AdCC), and intestinal type adenocarcinoma (ITAC) [ 22 – 24 ]. Although the literature is controversial regarding SOX2 amplification/Sox2 expression, recent data highlight the driver role of SOX2 in stemness with Sox2 overexpression and poor outcomes in patients with solid tumors [25] . Sox2 expression is also associated with resistance to chemotherapy through a plethora of mechanisms, and as such is a promising target for anticancer therapy [22 , 26] .…”

Sox2 and βIII-Tubulin as Biomarkers of Drug Resistance in Poorly Differentiated Sinonasal Carcinomas

“…The relation of Sox2 expression (and SOX2 gene copy number gain) with clinical outcomes is still a matter of debate, suggesting distinct roles for SOX2 depending on the tumor localization and histology. However, in a recent meta-analysis [33], a high expression level of Sox2 was significantly associated with poor outcomes in patients with solid tumors, which is consistent with a role as a transcription factor that induces stemness [34]. Sox2 expression is also associated with resistance to chemotherapy through a plethora of mechanisms and, as such, is a promising target for anticancer therapy [17,34].…”

“…However, in a recent meta-analysis [33], a high expression level of Sox2 was significantly associated with poor outcomes in patients with solid tumors, which is consistent with a role as a transcription factor that induces stemness [34]. Sox2 expression is also associated with resistance to chemotherapy through a plethora of mechanisms and, as such, is a promising target for anticancer therapy [17,34].…”

“…Hence, Sox2 expression appears to be a frequent event in sinonasal tumors. Most studies on SOX2 have concluded that protein overexpression is significantly correlated with tumor recurrence and poor prognosis [59,60], which is compatible with its function as a transcription factor linked to stemness [34]. However, the role of SOX2 is still controversial, as there have been other studies that did not reach the same conclusions [22,29].…”

Decoding the research landscape of drug resistance and therapeutic approaches in head and neck cancer: a bibliometric analysis from 2000 to 2023

“…#1 focuses on cancer stem cells, #2-#6 reflect hot topics, while #7 involves Ferroptosis and Cisplatin Resistance, and #8 may involve laryngeal squamous carcinoma drug resistance with the ERK pathway (Kim et al, 2012). Chemotherapeutic agents may increase stem-like cells in cancer tissue (Dorna and Paluszczak, 2023). Therefore, combining conventional chemotherapeutic agents with stemness modulators inhibits cancer cell proliferation and reduces recurrence.…”