The DNA Damage Response Is Differentially Involved in HPV-Positive and HPV-Negative Radioresistant Head and Neck Squamous Cell Carcinoma.
HPV
head and neck cancer
radioresistance
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
23 Jul 2021
23 Jul 2021
Historique:
received:
22
06
2021
revised:
21
07
2021
accepted:
21
07
2021
entrez:
7
8
2021
pubmed:
8
8
2021
medline:
8
8
2021
Statut:
epublish
Résumé
Radioresistance is a major cause of recurrences and radiotherapy (RT) failure in head and neck squamous cell carcinoma (HNSCC). DNA damage response (DDR) is known to be important for RT response, but its role in radioresistance is not fully understood. Here, we assessed the role of DDR in the radioresistance process of HNSCC by generating radioresistant clones from both HPV-positive SCC154 and HPV-negative SCC61 cells. We show that fractionated RT decreased RT response of HPV-positive and HPV-negative radioresistant clones in vitro and in vivo. Moreover, HPV-positive and HPV-negative radioresistant clones were characterized by differential DDR response. HPV-positive radioresistant clones showed less residual double-strand break damage and increased G2/M arrest recovery after RT, indicating an acquisition of increased DDR kinetics. In contrast, HPV-negative radioresistant clones showed less micronucleated cells after RT and increased survival upon checkpoint inhibition, indicating an increased replicative capacity. Inhibiting key factors of DDR in combination with RT rescued the radioresistant phenotype of both HPV-positive and HPV-negative radioresistant clones. Altogether, our results not only highlight the importance of DDR response in the radioresistance process of HPV-positive and HPV-negative HNSCC, but also provide possibilities for new therapies for HNSCC patients in recurrent settings.
Identifiants
pubmed: 34359617
pii: cancers13153717
doi: 10.3390/cancers13153717
pmc: PMC8345136
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : by Emmanuel van der Schueren fellowship for postdoctoral researchers from Kom op Tegen Kanker
ID : NA
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1521019N
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