Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment

Feng Ming Hsu, Shichuan Zhang, Benjamin P C Chen

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22-34
Number of pages13
JournalTranslational Cancer Research
Volume1
Issue number1
DOIs
StatePublished - Jun 1 2012

Keywords

  • Anti-DNA-PKcs strategies
  • Carcinogenesis
  • DNA damage

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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