title: Poly (ADP-ribose) polymerase inhibitor: an evolving paradigm in the treatment of prostate cancer.
abstract: Recent phase I studies have reported single-agent activities of poly (ADP-ribose) polymerase (PARP) inhibitor in sporadic and in BRCA-mutant prostate cancers. Two of the most common genetic alterations in prostate cancer, ETS gene rearrangement and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in preclinical models. Emerging evidence also suggests that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor (AR) and ETS gene rearrangement. In this article, the preclinical work and early-phase clinical trials in developing PARP inhibitor-based therapy as a new treatment paradigm for metastatic prostate cancer are reviewed.
authors.affiliation: Department of Genitourinary Oncology and Department of Cancer Imaging and Metabolism, H Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jingsong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D024682:BRCA2 Protein / Q000235:genetics; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D050783:Proto-Oncogene Proteins c-ets; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human