DNA-PK, a pharmacological target in cancer chemotherapy and radiotherapy?

Abstract

In the search for ways of sensitizing tumor cells to chemotherapy or radiotherapy, the inhibition of DNA repair has recently been proposed as a target of clinical interest. Ionizing radiation, as well as several antitumor drugs, induce the formation of DNA double-strand breaks (DSBs), that are highly damaging to the DNA, leading to cell death and genomic instability. DSBs are mainly repaired by the Non-Homologous End-Joining (NHEJ) process, in which DNA dependent protein kinase (DNA-PK) is the key complex. Consequently, specific DNA-PK inhibitors have been selected and evaluated for sensitizing cells to chemotherapy or radiotherapy. The choice of DNA-PK as a pharmacological target of interest in cancer treatment is discussed. © 2011 Salles B, et al.