Title:NF-κB Inhibitors in Head and Neck Cancer
Volume: 14
Issue: 5
Author(s): Siddavaram Nagini*, Kranthi Kiran Kishore Tanagala and Indranil Chattopadhyay
Affiliation:
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar- 608 002, Tamil Nadu,India
Keywords:
Bortezomib, cancer hallmarks, chemosensitivity, head and neck squamous cell carcinoma, NF-κB, NF-κB
inhibitors, radiosensitivity.
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.
