DNA end-processing enzyme polynucleotide kinase as a potential target in the treatment of cancer.
Pharmacological inhibition of DNA-repair pathways as an approach for the potentiation of chemo- and radio-therapeutic cancer treatments has attracted increasing levels of interest in recent years. Inhibitors of several enzymes involved in the repair of DNA strand breaks are currently at various stages of the drug development process. Polynucleotide kinase (PNK), a bifunctional DNA-repair enzyme that possesses both 3'-phosphatase and 5'-kinase activities, plays an important role in the repair of both single strand and double strand breaks and as a result, RNAi-mediated knockdown of PNK sensitizes cells to a range of DNA-damaging agents. Recently, a small molecule inhibitor of PNK has been developed that is able to sensitize cells to ionizing radiation and the topoisomerase I poison, camptothecin. Although still in the early stages of development, PNK inhibition represents a promising means of enhancing the efficacy of existing cancer treatments.
School of Health & Medicine, Division of Biomedical & Life Sciences, Lancaster University, Lancaster LA14YQ, UK. s.allinson@lancaster.ac.uk
Sarah L
SL
Allinson
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005544:Forecasting; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000502:physiology; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000037:antagonists & inhibitors* / Q000502:physiology; D017434:Protein Structure, Tertiary; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; C530380:PNKP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); D011116:Polynucleotide 5'-Hydroxyl-Kinase; D045643:DNA Repair Enzymes