"Back to a false normality": New intriguing mechanisms of resistance to PARP inhibitors

Risultato della ricerca: Article

6 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)23891-23904
Numero di pagine14
RivistaOncotarget
Volume8
Stato di pubblicazionePublished - 2017

Fingerprint

Neoplasms
Mutation
Homologous Recombination
Combination Drug Therapy
Antineoplastic Agents
Ovarian Neoplasms
Clinical Trials
Breast Neoplasms
Enzymes
Poly(ADP-ribose) Polymerase Inhibitors
Therapeutics
Clinical Studies
Synthetic Lethal Mutations

All Science Journal Classification (ASJC) codes

  • Oncology

Cita questo

@article{daa06eef19224e338168c471a505afce,
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.",
keywords = "BRCA1-2, PARP inhibitors, Resistance",
author = "Viviana Bazan and Antonio Russo and Lorena Incorvaia and Angela Listi' and Antonio Galvano and Marcello Ciaccio and Nadia Barraco and Valentina Calo' and Francesco Passiglia and Clara Natoli and Sergio Rizzo",
year = "2017",
language = "English",
volume = "8",
pages = "23891--23904",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",

}

TY - JOUR

T1 - "Back to a false normality": New intriguing mechanisms of resistance to PARP inhibitors

AU - Bazan, Viviana

AU - Russo, Antonio

AU - Incorvaia, Lorena

AU - Listi', Angela

AU - Galvano, Antonio

AU - Ciaccio, Marcello

AU - Barraco, Nadia

AU - Calo', Valentina

AU - Passiglia, Francesco

AU - Natoli, Clara

AU - Rizzo, Sergio

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - BRCA1-2

KW - PARP inhibitors

KW - Resistance

UR - http://hdl.handle.net/10447/229143

UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=14409&path%5B%5D=45959

M3 - Article

VL - 8

SP - 23891

EP - 23904

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

ER -