PARP Inhibitors Resistance: Mechanisms and Perspectives

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

doi:10.3390/cancers14061420

Cancers (Mar 2022)

PARP Inhibitors Resistance: Mechanisms and Perspectives

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

Affiliations

Elena Giudice: Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy
Marica Gentile: Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy
Vanda Salutari: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Caterina Ricci: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Lucia Musacchio: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Maria Vittoria Carbone: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Viola Ghizzoni: Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy
Floriana Camarda: Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy
Francesca Tronconi: Medical Oncology, Università Politecnica delle Marche, Via Tronto 10/a, 60126 Ancona, Italy
Camilla Nero: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Francesca Ciccarone: Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy
Giovanni Scambia: Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy
Domenica Lorusso: Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy

DOI: https://doi.org/10.3390/cancers14061420
Journal volume & issue: Vol. 14, no. 6
p. 1420

Abstract

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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.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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