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PARP Inhibitors Resistance: Mechanisms and Perspectives

by Giudice, Elena , Scambia, Giovanni , Ricci, Caterina , Gentile, Marica , Musacchio, Lucia , Carbone, Maria Vittoria , Nero, Camilla , Tronconi, Francesca , Camarda, Floriana , Salutari, Vanda , Ghizzoni, Viola , Ciccarone, Francesca , Lorusso, Domenica

in Apoptosis / Biomarkers / Cancer therapies / Clinical medicine / Disease resistance / DNA damage / DNA methylation / DNA polymerase / Genes / Genomes / Homologous recombination / Lethality / Mutation / Ovarian cancer / Patients / Poly(ADP-ribose) polymerase / Prognosis / Prostate / Proteins / Radiation / Review / Ribose / Tumors

2022

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2022

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2022

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Journal Article

PARP Inhibitors Resistance: Mechanisms and Perspectives

Giudice, Elena,

Scambia, Giovanni,

Ricci, Caterina,

Gentile, Marica,

Musacchio, Lucia,

Carbone, Maria Vittoria,

Nero, Camilla,

Tronconi, Francesca,

Camarda, Floriana,

Salutari, Vanda,

Ghizzoni, Viola,

Ciccarone, Francesca,

Lorusso, Domenica

2022

Overview

PolyADP-ribose polymerase (PARP) inhibitors (PARPis) represent the first clinically approved drugs able to provoke “synthetic lethality” in patients with homologous recombination-deficient (HRD) tumors. Four PARPis have just received approval for the treatment of several types of cancer. Besides, another three additional PARPis underlying the same mechanism of action are currently under investigation. Despite the success of these targeted agents, the increasing use of PARPis in clinical practice for the treatment of different tumors raised the issue of PARPis resistance, and the consequent disease relapse and dismal prognosis for patients. Several mechanisms of resistance have been investigated, and ongoing studies are currently focusing on strategies to address this challenge and overcome PARPis resistance. This review aims to analyze the mechanisms underlying PARPis resistance known today and discuss potential therapeutic strategies to overcome these processes of resistance in the future.

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MDPI AG,MDPI

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