抗辐射性
头颈部鳞状细胞癌
DNA损伤
癌症研究
辐射敏感性
DNA修复
放射治疗
头颈部癌
生物
癌症
奥拉帕尼
医学
肿瘤科
内科学
聚ADP核糖聚合酶
DNA
聚合酶
遗传学
作者
Maria Rita Fabbrizi,Jason L. Parsons
出处
期刊:Cancer drug resistance
[OAE Publishing Inc.]
日期:2020-01-01
被引量:11
摘要
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 in vitro and in vivo 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.
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