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

查看全文 作　　者：Maria Rita [1]Fabbrizi;Jason [1,2]L.Parsons

机构地区：[1]Cancer Research Centre,Department of Molecular and Clinical Cancer Medicine,University of Liverpool,Liverpool L39TA,United Kingdom;[2]Clatterbridge Cancer Centre NHS Foundation Trust,Clatterbridge Road,Bebington CH634JY,United Kingdom

出　　处：《Cancer Drug Resistance》索引2020年第3卷第4期,共16页

基　　金：Fabbrizi MR and Parsons JL are supported by North West Cancer Research(No.CR1197). 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. 关键词：DNA damage DNA repair head and neck cancer ionising radiation proton beam therapy RADIOBIOLOGY RADIOTHERAPY

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

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