Emerging Strategies against Head & Neck Cancer – A Review

Epigenetic Mechanisms in Head and Neck Cancer

“…Recently, promoter hypermethylation has been implicated in the down-regulation of PTEN in HNSCC cell lines. [72] HNSCCs also exhibit many chromosomal abnormalities, including amplifications of the 11q13 region containing the cyclin D1 gene and the 7p11 region encoding EGFR, which lead to protooncogene activation. [73] The most critical point in regulation of the cell cycle is the G1 checkpoint.…”

“…The constitutive EGFR activation caused via autocrine stimulation and through the coexpression of EGFR with its ligands, TGFα, has been observed and is indicative of its poor prognosis. [72] EGFR-targeted therapy is commonly used for the treatment of advanced HNSCC due to numerous findings that describe overexpression and/or high activity of EGFR in the majority of HNSCC. [80] Various factors are known to regulate angiogenesis; for example, vascular endothelial cell growth factor (VEGF) has potent angiogenic effects.…”

“…The presence of VEGF has been reported in approximately 40% of head and neck squamous cell carcinomas (HNSCCs), and its presence is associated with a poor prognosis. [72] Other mechanisms included in the tumorous angiogenesis lie in the intake and utilization of locally stored fibroblast growth factors (FGFs). [50] FGF-1 (aFGF) and FGF-2 (bFGF) are found in most embryonic and adult normal and tumor tissues, where they are immobilized in the extracellular matrix (ECM).…”

“…[88] The hypermethylated adenomatosis polyposis coli (APC) tumor suppressor gene has reduced expression levels along with loss of heterozygosity (LOH), leading to the altered functioning of the APC tumor suppressor proteins, which play a role for the integrity and function of the β-catenin destruction complex. [72] The APC protein, a negative regulator of this pathway, has been strongly implicated in the development of colon cancer but still has an undetermined role in the formation of oral cancer. [89] Loss of heterozygosity of the APC gene and epigenetic events lead to the decreased expression of APC and the Wnt antagonists, the secreted frizzled-related proteins (SFRPs), Wnt inhibitory factors (WIFs), and Dickkopf family members (DKKs), primarily by promoter hypermethylation.…”