Targeting poly (ADP) ribose polymerase I (PARP-1) and PARP-1 interacting proteins for cancer treatment.
Cancer is a disease of uncontrolled cellular proliferation. Chemotherapy and radiation therapy are the two main modalities for cancer treatment. However, some cancer types have been found to be refractory to these treatments. Additionally, certain chemicals that are used in clinical trials produce high cytotoxicity as a secondary effect. Hence, current research is focused on finding ways by which cancer cells can be specifically sensitized to apoptotic death with minimal or no secondary effects on normal healthy cells. Since the resistance of cancer cells to DNA damaging agents stems from the modulation of DNA repair pathways, pharmacological inhibition of these pathways has been emerging as an effective tool for cancer treatment. Inhibition of key proteins involved in the molecular cascade of DNA damage detection and repair such as poly (ADP) ribose polymerase I (PARP-1) and its interacting proteins [DNA dependent protein kinase (DNA-PK) and Cockayne syndrome group B (CSB)] has recently proven to be successful for the treatment of various types of cancer cells and tumor xenografts in vitro. This review summarizes some of the recent findings and the potential application of DNA repair inhibitors in cancer treatment.
Sakamoto-Hojo
Elza T
ET
Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
Balajee
Adayabalam S
AS
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D051747:DNA-Activated Protein Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D051747:DNA-Activated Protein Kinase