The DNA repair complex DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy.
A line of investigation in the search for sensitizing tumor cells to chemotherapy or radiotherapy relies on the selection of DNA repair inhibitors. In the area of DNA repair mechanisms, DNA-dependent protein kinase (DNA-PK) represents a key complex. Indeed DNA-PK is involved in the non-homologous end joining (NHEJ) process that corresponds to the major activity responsible for cell survival after ionizing radiation or chemotherapeutic treatment producing DNA double strand breaks. DNA-PK belongs to the PI3-K related kinase family and specific inhibitors have been recently selected and evaluated as radio- and chemo-sensitizers. These drugs, along with other ways to inhibit the DSBs repair process, are presented and discussed.
Institut de Pharmacologie et Biologie Structurale (IPBS) UMR CNRS 5089, Toulouse, France. bernard.salles@ipbs.fr
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Salles
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Calsou
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Muller
D002135:Calcium-Binding Proteins / Q000187:drug effects* / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D051747:DNA-Activated Protein Kinase