Nanotechnology in Cancer Therapy: Targeting the Inhibition of Key DNA Repair Pathways

K.      Aziz; S.      Nowsheen; A.      G. Georgakilas

doi:10.2174/156652410792630599

Abstract

Cancer therapy has been changing over the decades as we move away from the administration of broad spectrum cytotoxic drugs and towards the use of therapy targeted for each tumor type. After the induction of DNA damage through chemotherapeutic agents, tumor cells can survive due to their proficient DNA repair pathways, some of which are dysregulated in cancer. Latest improvements in nanotechnology and drug discovery have led to the discovery of some very unique, highly specific and innovative drugs as inhibitors of various DNA repair pathways like base excision repair and double strand break repair. In this review we look at the efficacy and potency of these small chemical molecules to target the processing of DNA damage induced by standard therapeutic agents. Emphasis is given to those drugs currently under clinical trials. We also discuss the future directions of using this nanotechnology to increase the therapeutic ratio in cancer treatment.

Keywords: Cancer therapy, DNA damage, DNA repair, inhibitors, nanotechnology, base excision repair, double strand break repair, Ionizing rad, Radon decay, Cosmic rays, Non-ionizing radiations (UV), Free radicals, ROS, RNS, Glutathione, Antioxidant, Superoxide dismutase, Catalase, Glutathione peroxidase, Genome, Homeostasis, Radiomimetic drugs, Bleomycin, Neocarzinostatin, Genotoxic agents, Oxypurines, Oxypyrimidines, Oxybases, Glycosylases, Endonucleases, Estrogen, Mutagenesis, Carcinogenesis, Polymerase, Tumor cells, Apoptosis, Discovery, Methotrexate, Hydroxyurea, Taxol, X-rays, a-particles, Polynucleotide kinase, PARP, Nitric oxide synthase, ABT- 888, Temozolomide, PARP inhibitor, BSI-201, Cyclophosphamide, AZD2281, carboplatin, KU005868, TRC102, Pemetrexed, Radioresistance, Squamous cell carcinoma, Melanoma, Glioblastoma, pyridinylfuranopyrimidine inhibitor, lithium, Erlotinib, autophosphorylation