title: "Back to a false normality": new intriguing mechanisms of resistance to PARP inhibitors.
abstract: Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD). This review summarizes the biological background underlying PARP-inhibition, reporting the results of the most relevant clinical trials carried out in patients treated with PARP inhibitors alone or in combination with chemotherapy. Molecular mechanisms responsible for the occurrence of both primary and acquired resistance have been elucidated, in order to support the development of new treatment strategies.
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Incorvaia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Francesc
authors.initials: F
authors.lastname: Passiglia
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Galvano
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Listì
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barraco
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Maragliano
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Calò
authors.affiliation: Department of Medical, Oral and Biotechnological Sciences, Centre of Ageing Sciences and Translational Medicine - CESI-MeT University "G. D'Annunzio", Chieti, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Natoli
authors.affiliation: Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnology, University of Palermo - U.O.C. Laboratory Medicine - CoreLab, Policlinico University Hospital, Palermo, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ciaccio
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Bazan
authors.affiliation: Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism; D024682:BRCA2 Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009154:Mutation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
keywords: BRCA1-2; PARP inhibitors; resistance