PARP Inhibitors Resistance: Mechanisms and Perspectives

Cancers

Marica Gentile¹  Maria Vittoria Carbone²  Francesca Ciccarone²  Camilla Nero²  Caterina Ricci²  Lucia Musacchio²  Vanda Salutari²  Domenica Lorusso³  Viola Ghizzoni³  Elena Giudice³  Giovanni Scambia³  Floriana Camarda⁴  Francesca Tronconi⁵ 

[1] Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy;Department of Woman, Child and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy;Institute of Obstetrics and Gynecology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy;Medical Oncology, Università Cattolica del Sacro Cuore, Largo Agostino Gemelli 8, 00168 Rome, Italy;Medical Oncology, Università Politecnica delle Marche, Via Tronto 10/a, 60126 Ancona, Italy;

关键词: ovarian cancer;    polyADP-ribose polymerase (PARP) inhibitor;    PARP inhibitor resistance;    DNA damage repair;    homologous recombination;    BRCA;   

DOI  :  10.3390/cancers14061420

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown