EGFR overexpression increases radiotherapy response in HPV-positive head and neck cancer through inhibition of DNA damage repair and HPV E6 downregulation

HGF/MET Signalling and DNA Damage Response: Strategies to Conquer Radiotherapy Resistance in Head and Neck Cancer

“…Nonetheless, using combinational therapy reduces the clinical translatability of our conjecture since increasing the number of inhibitors could increase the likelihood of toxicity. Furthermore, others have shown inhibition of CHK1 to potentiate effects of DDAs irrespective of p53 status [144,145]. This indicates that other determinants aside from p53 including (epi) genetics, Rb, p16, and Wee1 will influence treatment.…”

EGFR Mutations in Head and Neck Squamous Cell Carcinoma

“…Additionally, HPV E16 levels were significantly suppressed in EGFR overexpressing HPV-positive cells resulting in restoration of p53 activity leading to RT sensitivity. When EGFR was inhibited using the TKI Gefitinib, it led to radiosensitization, further confirming that EGFR expression has a vital role in RT response [ 62 ].…”

“…The activation of autophagy has been shown to have opposing roles with respect to radiation response with some reports showing autophagy to be a radiosensitizer [ 59 , 60 ], while others show it plays a role in radioresistance [ 61 ]. Interestingly, a recent study found that EGFR expression and RT response depended on the human papilloma virus (HPV) status of the tumors [ 62 ]. In HPV-negative HNSCC cells, EGFR overexpression conferred increased survival, epithelial-to-mesenchymal transition and radioresistance via activation of vital DSB repair proteins post-irradiation.…”

Development and Evaluation of Targeted Optical Imaging Probes for Image‐Guided Surgery in Head and Neck Cancer

“…The EGFR, which is also known as HER1 or ErbB1, [ 103 ] is a transmembrane receptor that consists of three parts: extracellular, transmembrane, and intracellular domains. It is overexpressed in more than 90% of HNSCC patients, [ 104 ] and is mostly detected in advanced stages. [ 105 ] In an analysis of the relationship among CD44, EGFR, and p16 in 64 samples of HNSCC patients, 45.3% showed strong EGFR expression both in the membrane and cytoplasm, and 23.4% showed strong expression in the membrane.…”