Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target.
Inhibitors of various elements of the DNA repair pathways have entered clinical development or are in late preclinical stages of drug development. It was initially considered that agents targeting DNA repair would act to overcome tumor resistance to chemotherapy and radiotherapy. More recent data have shown that targeting DNA repair pathways can be effective in selected tumors via a synthetically lethal route, with single agent activity having been shown with poly-ADP ribose polymerase (PARP) inhibitors. An increased understanding of the biology and interaction of the DNA repair pathways also means that rational combination of DNA repair inhibitors may also give great benefit in the clinic.
Plummer
Ruth
R
Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom. Ruth.plummer@ncl.ac.uk
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D055808:Drug Discovery / Q000379:methods / Q000639:trends*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D045643:DNA Repair Enzymes