title: The role of PARP in DNA repair and its therapeutic exploitation.
abstract: Historically, PARP inhibitors (PARPi) were developed to potentiate the cytotoxic effect of certain chemotherapeutic agents and are currently being investigated in combination with chemotherapy in diverse cancer types. These agents are also radiosensitisers and clinical trials of PARPi with concurrent radiation are required. It has long been recognised that defective DNA repair pathways lead to tumour susceptibility. Recent studies indicate that tumour cells with defective homologous recombination (HR) repair pathways, the classic example being BRCA mutations, are exquisitely sensitive to PARPi. Defects in HR are not restricted to BRCA-associated tumours and other cancer types may be enriched for HR defects and hence susceptible to PARP inhibition. The identification of predictive markers for sensitivity to PARP inhibition is a priority area for research.
authors: UT-MD Anderson Cancer Centre, Department of Gastrointestinal Medical Oncology, 1515 Holcombe Boulevard, Unit 426, Houston, TX 77030, USA.
authors: M
authors: M
authors: Javle
authors: N J
authors: NJ
authors: Curtin
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents; D011065:Poly(ADP-ribose) Polymerases