Radiation Resistance in Head and Neck Squamous Cell Carcinoma: Dire Need for an Appropriate Sensitizer

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2020 Mar 12

PMID 32157215

Citations 61

Authors

Marsha-Kay N D Hutchinson

Michelle Mierzwa

Nisha J DSilva

Affiliations

Soon will be listed here.

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.

Citing Articles

Radioresistance in Hepatocellular Carcinoma: Biological Bases and Therapeutic Implications.

Wu J, Zhao X, Ren B, Duan X, Sun J Int J Mol Sci. 2025; 26(5).

PMID: 40076465 PMC: 11899467. DOI: 10.3390/ijms26051839.

Deciphering the prognostic potential of a necroptosis-related gene signature in head and neck squamous cell carcinoma: a bioinformatic analysis.

Wang S, Jiang J, Xing M, Su H Transl Cancer Res. 2025; 14(1):340-353.

PMID: 39974401 PMC: 11833364. DOI: 10.21037/tcr-24-743.

Targeting Fibroblast-Derived Interleukin 6: A Strategy to Overcome Epithelial-Mesenchymal Transition and Radioresistance in Head and Neck Cancer.

Li X, Escoffier H, Sauter T, Tavassoli M Cancers (Basel). 2025; 17(2).

PMID: 39858048 PMC: 11763410. DOI: 10.3390/cancers17020267.

Combinatorial functionomics identifies HDAC6-dependent molecular vulnerability of radioresistant head and neck cancer.

Chan S, Yeo C, Hong B, Tan E, Beh C, Yeo E Exp Hematol Oncol. 2025; 14(1):5.

PMID: 39800760 PMC: 11727331. DOI: 10.1186/s40164-024-00590-8.

Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons.

Barham W, Stagg M, Mualla R, DiLeo M, Kansara S Cancers (Basel). 2025; 17(1.

PMID: 39796771 PMC: 11720666. DOI: 10.3390/cancers17010144.

References

Gunn G, Blanchard P, Garden A, Zhu X, Fuller C, Mohamed A . Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma. Int J Radiat Oncol Biol Phys. 2016; 95(1):360-367. PMC: 5474303. DOI: 10.1016/j.ijrobp.2016.02.021. View

Patel S, Wang Z, Wong W, Murad M, Buckey C, Mohammed K . Charged particle therapy versus photon therapy for paranasal sinus and nasal cavity malignant diseases: a systematic review and meta-analysis. Lancet Oncol. 2014; 15(9):1027-38. DOI: 10.1016/S1470-2045(14)70268-2. View

Oksuz D, Prestwich R, Carey B, Wilson S, Senocak M, Choudhury A . Recurrence patterns of locally advanced head and neck squamous cell carcinoma after 3D conformal (chemo)-radiotherapy. Radiat Oncol. 2011; 6:54. PMC: 3127781. DOI: 10.1186/1748-717X-6-54. View

De Felice F, Thomas C, Barrington S, Pathmanathan A, Lei M, Urbano T . Analysis of loco-regional failures in head and neck cancer after radical radiation therapy. Oral Oncol. 2015; 51(11):1051-1055. DOI: 10.1016/j.oraloncology.2015.08.004. View

Fakhry C, Zhang Q, Gillison M, Nguyen-Tan P, Rosenthal D, Weber R . Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: Implications for risk-based therapeutic intensity trials. Cancer. 2019; 125(12):2027-2038. PMC: 6594017. DOI: 10.1002/cncr.32025. View

Kolesnick , FUKS . Modulation of the Apoptotic Response: Potential for Improving the Outcome in Clinical Radiotherapy. Semin Radiat Oncol. 1996; 6(4):273-283. DOI: 10.1053/SRAO00600273. View

De Crevoisier R, Domenge C, Wibault P, Koscielny S, Lusinchi A, Janot F . Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma. Cancer. 2001; 91(11):2071-6. DOI: 10.1002/1097-0142(20010601)91:11<2071::aid-cncr1234>3.0.co;2-z. View

Janot F, De Raucourt D, Benhamou E, Ferron C, Dolivet G, Bensadoun R . Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma. J Clin Oncol. 2008; 26(34):5518-23. DOI: 10.1200/JCO.2007.15.0102. View

Hanai R, Yazu M, Hieda K . On the experimental distinction between ssbs and dsbs in circular DNA. Int J Radiat Biol. 1998; 73(5):475-9. DOI: 10.1080/095530098142013. View

10.

Rothkamm K, Lobrich M . Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci U S A. 2003; 100(9):5057-62. PMC: 154297. DOI: 10.1073/pnas.0830918100. View

11.

Cadet J, Douki T, Ravanat J . Oxidatively generated damage to the guanine moiety of DNA: mechanistic aspects and formation in cells. Acc Chem Res. 2008; 41(8):1075-83. DOI: 10.1021/ar700245e. View

12.

Dynan W, Takeda Y, Roth D, Bao G . Understanding and re-engineering nucleoprotein machines to cure human disease. Nanomedicine (Lond). 2008; 3(1):93-105. PMC: 2766608. DOI: 10.2217/17435889.3.1.93. View

13.

Zhao X, Wei C, Li J, Xing P, Li J, Zheng S . Cell cycle-dependent control of homologous recombination. Acta Biochim Biophys Sin (Shanghai). 2017; 49(8):655-668. DOI: 10.1093/abbs/gmx055. View

14.

Emerson C, Bertuch A . Consider the workhorse: Nonhomologous end-joining in budding yeast. Biochem Cell Biol. 2016; 94(5):396-406. PMC: 5367924. DOI: 10.1139/bcb-2016-0001. View

15.

Reynolds P, Anderson J, Harper J, Hill M, Botchway S, Parker A . The dynamics of Ku70/80 and DNA-PKcs at DSBs induced by ionizing radiation is dependent on the complexity of damage. Nucleic Acids Res. 2012; 40(21):10821-31. PMC: 3510491. DOI: 10.1093/nar/gks879. View

16.

Stucki M, Jackson S . gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair (Amst). 2006; 5(5):534-43. DOI: 10.1016/j.dnarep.2006.01.012. View

17.

Deng C, Zhang P, Harper J, Elledge S, Leder P . Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell. 1995; 82(4):675-84. DOI: 10.1016/0092-8674(95)90039-x. View

18.

Lafarga V, Cuadrado A, Lopez de Silanes I, Bengoechea R, Fernandez-Capetillo O, Nebreda A . p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint. Mol Cell Biol. 2009; 29(16):4341-51. PMC: 2725730. DOI: 10.1128/MCB.00210-09. View

19.

Deckbar D, Stiff T, Koch B, Reis C, Lobrich M, Jeggo P . The limitations of the G1-S checkpoint. Cancer Res. 2010; 70(11):4412-21. DOI: 10.1158/0008-5472.CAN-09-3198. View

20.

Chan T, Hwang P, Hermeking H, Kinzler K, Vogelstein B . Cooperative effects of genes controlling the G(2)/M checkpoint. Genes Dev. 2000; 14(13):1584-8. PMC: 316737. View