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Review
. 2020 Apr;39(18):3638-3649.
doi: 10.1038/s41388-020-1250-3. Epub 2020 Mar 10.

Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer

Marsha-Kay N D Hutchinson  1 , Michelle Mierzwa  2 , Nisha J D'Silva  3   4
Affiliations
Review

Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer

Marsha-Kay N D Hutchinson et al. Oncogene. 2020 Apr.

Abstract

Radiation is a significant treatment for patients with head and neck cancer. Despite advances to improve treatment, many tumors acquire radiation resistance resulting in poor survival. Radiation kills cancer cells by inducing DNA double-strand breaks. Therefore, radiation resistance is enhanced by efficient repair of damaged DNA. Head and neck cancers overexpress EGFR and have a high frequency of p53 mutations, both of which enhance DNA repair. This review discusses the clinical criteria for radiation resistance in patients with head and neck cancer and summarizes how cancer cells evade radiation-mediated apoptosis by p53- and epidermal growth factor receptor (EGFR)-mediated DNA repair. In addition, we explore the role of cancer stem cells in promoting radiation resistance, and how the abscopal effect provides rationale for combination strategies with immunotherapy.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Role of radiation in treatment of HNSCC based on stage.
Early stage disease is treated with a unimodality approach while later stage disease requires a multimodality approach.
Fig. 2
Fig. 2. Major steps in NHEJ repair.
Broken DNA ends are protected by Ku70/80 before the recruitment of DNA/PKcs and processing by artemis. Damaged bases are replaced and broken ends are ligated.
Fig. 3
Fig. 3. p53 determines cell fate following induction of DNA damage.
Activation of ATM activates p53, which depending on severity of the damage executes one of the two functions: cell-cycle arrest or apoptosis. Cells undergo cell-cycle arrest if damage is repairable and apoptose if irreparable.
See this image and copyright information in PMC

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