Inhibition of DNA synthesis and cancer therapies

Abstract

Cancer is a worldwide problem afflicting 19 million people. Inhibition of DNA synthesis has been a cornerstone of anticancer therapy. A variety of chemotherapy drugs have been developed and many of these are aimed at inhibiting DNA synthesis, as they damage DNA, form DNA adduct and interfere with DNA synthesis. Another type of chemotherapy interferes with the synthesis of nucleotide pools. There are also other types of drugs that inhibit topoisomerases resulting in the interference with DNA replication and transcription. Significant progress has been made regarding radiation therapy that includes X-ray (and γ-ray), proton therapy and heavy ion therapy. The Auger therapy is a type of radiation therapy that differs from X-ray, proton or heavy ion therapy. The method relies on the use of high Z elements such as gadolinium, iodine, gold or silver. Irradiation of these elements results in the release of electrons including the Auger electrons that have strong DNA damaging effect. Tamanoi et al. developed novel nanoparticles containing gadolinium or iodine to place high Z elements at the periphery of the nucleus thus localizing them close to DNA. Irradiation with monochromatic X-ray resulted in the formation of double-strand DNA breaks leading to the destruction of tumor mass. Comparison of conventional X-ray therapy and the Auger therapy is discussed.

Keywords: Auger therapy; Cancer; Chemotherapy; DNA damage; Inhibition of DNA synthesis; Nanoparticles containing gadolinium or iodine; Radiation therapy.