title: Targeting PARP in Prostate Cancer: Novelty, Pitfalls, and Promise.
abstract: Metastatic prostate cancer remains a highly lethal disease with no curative therapeutic options. A significant subset of patients with prostate cancer harbor either germline or somatic mutations in DNA repair enzyme genes such as BRCA1, BRCA2, or ATM. Emerging data suggest that drugs that target poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) enzymes may represent a novel and effective means of treating tumors with these DNA repair defects, including prostate cancers. Here we will review the molecular mechanism of action of PARP inhibitors and discuss how they target tumor cells with faulty DNA repair functions and transcriptional controls. We will review emerging data for the utility of PARP inhibition in the management of metastatic prostate cancer. Finally, we will place PARP inhibitors within the framework of precision medicine-based care of patients with prostate cancer.
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Palmbos
authors.forename: Maha H
authors.initials: MH
authors.lastname: Hussain
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D018579:Patient Selection; D010641:Phenotype; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057285:Precision Medicine; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D045643:DNA Repair Enzymes