Epigenetic aberrations, associated with altered DNA methylation profiles and global changes in the level of histone modifications, are commonly detected in head and neck squamous cell carcinomas (HNSCC). Recently, histone lysine demethylases have been implicated in the pathogenesis of HNSCC and emerged as potential molecular targets. Histone lysine demethylases (KDMs) catalyze the removal of methyl groups from lysine residues in histones. By affecting the methylation of H3K4, H3K9, H3K27, or H3K36, these enzymes take part in transcriptional regulation, which may result in changes in the level of expression of tumor suppressor genes and protooncogenes. KDMs are involved in many biological processes, including cell cycle control, senescence, DNA damage response, and heterochromatin formation. They are also important regulators of pluripotency. The overexpression of most KDMs has been observed in HNSCC, and their inhibition affects cell proliferation, apoptosis, cell motility, invasiveness, and stemness. Of all KDMs, KDM1, KDM4, KDM5, and KDM6 proteins are currently regarded as the most promising prognostic and therapeutic targets in head and neck cancers. The aim of this review is to present up-to-date knowledge on the significance of histone lysine demethylases in head and neck carcinogenesis and to discuss the possibility of using them as prognostic markers and pharmacological targets in patients’ treatment.
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.
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