Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment.
Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment.
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DOI：
10.3978/j.issn.2218-676x.2012.04.01
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发表时间：
2012-06-01
影响因子：
0.9
通讯作者：
Chen BP
中科院分区：
文献类型：
--
作者：
Hsu FM;Zhang S;Chen BP
DNA依赖性蛋白激酶催化亚基（DNA-PKcs）是非同源末端连接（NHEJ）途径的关键组分，参与DNA双链断裂修复、免疫活性、基因组完整性和表皮生长因子受体信号传导。临床研究表明，DNA-PKcs的表达和活性与癌症的进展和对治疗的反应相关。已经开发了各种抗DNA-PKcs策略，并在临床前研究中进行了测试，以利用DNA-PKcs抑制在放射治疗增敏和与其他抗肿瘤药物联合治疗中的益处。本文综述了DNA-PKcs与肿瘤发生发展的关系，并讨论了目前抑制DNA-PKcs的方法和机制。未来的挑战是了解DNA-PKcs活性如何与癌症易感性相关，并确定哪些患者最受益于DNA-PKcs抑制。
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. Clinical studies indicate that expression and activity of DNA-PKcs is correlated with cancer progression and response to treatment. Various anti-DNA-PKcs strategies have been developed and tested in preclinical studies to exploit the benefit of DNA-PKcs inhibition in sensitization of radiotherapy and in combined modality therapy with other antitumor agents. In this article, we review the association between DNA-PKcs and cancer development and discuss current approaches and mechanisms for inhibition of DNA-PKcs. The future challenges are to understand how DNA-PKcs activity is correlated with cancer susceptibility and to identify those patients who would most benefit from DNA-PKcs inhibition.