Abstract
Overexpression and aberrant activation of NF-κB has been extensively documented during the development and progression of head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer worldwide. Accumulating evidence indicates that NF-κB plays a central role in HNSCC development via regulation of a multitude of genes involved in cell proliferation, cell survival, apoptosis evasion, inflammation, immune functions, stress response, invasion, metastasis, angiogenesis and resistance to anticancer therapies. Different classes of drugs, chemicals, dietary agents, medicinal plants and phytochemicals have been demonstrated to inhibit NF-κB signalling at various levels including upstream of IKK, directly at the IKK complex, phosphorylation of IκB, ubiquitination or proteasomal degradation of IκB; nuclear translocation of NF-κB and binding of NF- κB to DNA. NF-κB expression has been suggested as a novel marker of chemo- and radiotherapy resistance. Downregulation or knockdown of NF-κB activators, combination chemotherapy, as well as natural products that inhibit NF-κB signalling confer chemoradiosensitivity. In particular, inhibition of proteasomal degradation of IκB has evolved as an important tool for pharmacological intervention. Further investigation to identify NF-κB inhibitors with greater specificity, efficacy and safety as well as strategies to intensify chemo-radiosensitivity will aid in the prevention and treatment of HNSCC.
Keywords: Bortezomib, cancer hallmarks, chemosensitivity, head and neck squamous cell carcinoma, NF-κB, NF-κB inhibitors, radiosensitivity.
Graphical Abstract
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