title: Poly (ADP-ribose) polymerase (PARP): rationale, preclinical and clinical evidences of its inhibition as breast cancer treatment.
abstract: BACKGROUND
  The chance to take advantage of genetic defects of cancer cells is a promising clinical tool in breast cancer therapy. Among the genetic aberrations, dysfunctions in DNA repair mechanisms are quite common and suitable for an attractive antitumor effect. Poly (ADP-ribose) polymerase I (PARP-1) is an enzyme with many functions in transcriptions and cell cycle regulation and in coordination of cellular response to DNA damage. Its involvement in tumorigenesis is witnessed by the overexpression found in different primary human tumors, where the increased enzymatic activity leads to cancer cell protection against DNA damage and instability. Therefore, activity of PARP and the opportunity to block it, mainly in cancer cells also deficient in other mechanisms of repair, are promising.
  
  
  METHODS
  In this review, areas covered include the main DNA repair mechanisms, the role of PARP enzymatic activity in diverse cell pathways as well as the preclinical and clinical data with PARP inhibitors.
  
  
  CONCLUSIONS
  Despite the theoretical role of PARP inhibitors as therapeutic strategy in specific subtypes of breast cancer (hereditary BRCA1/BRCA2 mutation-related cancers and sporadic triple-negative breast cancer), questions are still open. More exhaustive knowledge is needed about other important functions of PARPs in cellular homeostasis and about escape mechanisms of cancer cells to inhibitory effect of PARP inhibitors.
authors.affiliation: Medical Oncology Division & Breast Unit, Ospedale A. Perrino, Brindisi, Italy. laura.orlando68@gmail.com
authors.forename: Laura
authors.initials: L
authors.lastname: Orlando
authors.forename: Paola
authors.initials: P
authors.lastname: Schiavone
authors.forename: Palma
authors.initials: P
authors.lastname: Fedele
authors.forename: Nicola
authors.initials: N
authors.lastname: Calvani
authors.forename: Angelo
authors.initials: A
authors.lastname: Nacci
authors.forename: Margherita
authors.initials: M
authors.lastname: Cinefra
authors.forename: Maria
authors.initials: M
authors.lastname: D'Amico
authors.forename: Enrica
authors.initials: E
authors.lastname: Mazzoni
authors.forename: Antonella
authors.initials: A
authors.lastname: Marino
authors.forename: Francesco
authors.initials: F
authors.lastname: Sponziello
authors.forename: Franco
authors.initials: F
authors.lastname: Morelli
authors.forename: Lucia
authors.initials: L
authors.lastname: Lombardi
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinieri
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004260:DNA Repair; D005260:Female; D006801:Humans; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases