Radiotherapy and the cellular DNA damage response: current and future perspectives on head and neck cancer treatment

Fabbrizi, Maria Rita ORCID: 0000-0002-5156-1575 and Parsons, Jason L ORCID: 0000-0002-5052-1125 (2020) Radiotherapy and the cellular DNA damage response: current and future perspectives on head and neck cancer treatment. Cancer Drug Resistance, 3 (4). pp. 775-790.

Text Fabbrizi and Parsons CDR Rev2.docx - Author Accepted Manuscript Download (531kB)

Abstract

Incidences of head and neck squamous cell carcinoma (HNSCC) have been on the rise in the last few decades, with a significant risk factor being human papillomavirus (HPV) type-16/18 infection, particularly in the development of oropharyngeal cancers. Radiotherapy (RT) is an important treatment modality for HNSCC, where it promotes extensive cellular DNA damage leading to the therapeutic effect. It has been well-established that HPV-positive HNSCC display better response rates and improved survival following RT compared to HPV-negative HNSCC. The differential radiosensitivity has been largely associated with altered cellular DNA damage response mechanisms in HPV-positive HNSCC, and particularly with the signaling and repair of DNA double strand breaks. However, other factors, particularly hypoxia present within the solid cancer, have a major impact on relative radioresistance. Consequently, recent approaches aimed at enhancing the radiosensitivity of HNSCC have largely centered on targeting key proteins involved in DNA repair, DNA damage checkpoint activation, and hypoxia signaling. These studies have utilised <i>in vitro</i> and <i>in vivo</i> models of HPV-positive and HPV-negative HNSCC and examined the impact of specific inhibitors against the targets in combination with radiation in suppressing HNSCC cell growth and survival. Here, accumulating evidence has shown that targeting enzymes including poly (ADP-ribose) polymerase, ataxia telangiectasia and Rad-3 related, DNA-dependent protein kinase catalytic subunit, and checkpoint kinase 1 can radiosensitise HNSCC cells which should be taken forward in further preclinical studies, with the goal of optimizing the future effective RT treatment of HNSCC.

Item Type:	Article
Uncontrolled Keywords:	DNA damage, DNA repair, head and neck cancer, ionising radiation, proton beam therapy, radiobiology, radiotherapy
Depositing User:	Symplectic Admin
Date Deposited:	07 Oct 2020 08:26
Last Modified:	18 Jan 2023 23:29
DOI:	10.20517/cdr.2020.49
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3103810