DNA-PK, a Pharmacological Target in Cancer Chemotherapy and Radiotherapy?

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.