Abstract
Head and neck squamous carcinoma (HNSCC) is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs), a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors characterized by lesions in the oral cavity, larynx, pharynx, salivary glands, and thyroid [1,2,3]
We showed that reduction of H3K9ac is associated with increased cell proliferation and activation of epithelial-mesenchyme transition (EMT) during oral carcinogenesis, suggesting the involvement of H3K9ac in tumor progression of HNSCC [87,112]
We have recently found that changes in chromatin acetylation of HNSCC unexpectedly triggered the reduction of cancer stem cells (CSCs)
Summary
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors characterized by lesions in the oral cavity, larynx, pharynx (including nasopharynx, oropharynx, and hypopharynx), salivary glands, and thyroid [1,2,3]. Despite several efforts to identify biomarkers for early detection and develop new treatments, the overall survival rate and prognosis remain poor [2,6,7]. Cancer research efforts have focused on the genetic basis of tumor development and progression, identifying mutations and characterizing pathways that activate oncogenes and inactivate tumor suppressor genes. The research has pointed to epigenetic alterations as critic changes involved in the initiation and progression of human cancers [11]. Epigenetic modifications contribute to the cellular plasticity during tumor progression, and the formation of tumor-initiating cells or cancer stem cells (CSCs) [14,15,16,17,18]. We provide insights into recent studies on the epigenetics of CSCs, and novel treatment modalities using epigenetic drugs (Epi-drugs) alone, or in combination with conventional therapies
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