Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer : Quo Vadis?

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Boussios , S , Moschetta , M , Karihtala , P , Samartzis , E P , Sheriff , M , Pappas-Gogos , G , Ozturk , M A , Uccello , M , Karathanasi , A , Tringos , M , Rassy , E & Pavlidis , N 2020 , ' Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer : Quo Vadis? ' , Annals of translational medicine , vol. 8 , no. 24 , 1706 . https://doi.org/10.21037/atm.2020.03.156

Title: Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer : Quo Vadis?
Author: Boussios, Stergios; Moschetta, Michele; Karihtala, Peeter; Samartzis, Eleftherios P.; Sheriff, Matin; Pappas-Gogos, George; Ozturk, Mehmet Akif; Uccello, Mario; Karathanasi, Afroditi; Tringos, Michail; Rassy, Elie; Pavlidis, Nicholas
Contributor organization: Department of Oncology
HUS Comprehensive Cancer Center
University of Helsinki
Helsinki University Hospital Area
Date: 2020-12
Language: eng
Number of pages: 17
Belongs to series: Annals of translational medicine
ISSN: 2305-5839
DOI: https://doi.org/10.21037/atm.2020.03.156
URI: http://hdl.handle.net/10138/326843
Abstract: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality among women, potentially due to ineffectiveness of screening tests for early detection. Patients typically present with advanced disease at diagnosis, whereas, up to 80% relapse and the estimated median progression-free survival (PFS) is approximately 12-18 months. Increased knowledge on the molecular biology of EOC resulted in the development of several targeted therapies, including poly(ADP-ribose) polymerase (PARP) inhibitors. These agents have changed the therapeutic approach of the EOC and exploit homologous recombination (HR) deficiency through synthetic lethality, especially in breast cancer genes 1 and 2 (BRCA1/2) mutation carriers. Furthermore, BRCA wild-type patients with other defects in the HR repair pathway, or those with platinum-resistant tumors may obtain benefit from this treatment. While PARP inhibitors as a class display many similarities, several differences in structure can translate into differences in tolerability and antitumor activity. Currently, olaparib, rucaparib, and niraparib have been approved by Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) for the treatment of EOC, while veliparib is in the late stage of clinical development. Finally, since October 2018 talazoparib is FDA and EMA approved for BRCA carriers with metastatic breast cancers. In this article, we explore the mechanisms of DNA repair, synthetic lethality, efficiency of PARP inhibition, and provide an overview of early and ongoing clinical investigations of the novel PARP inhibitors veliparib and talazoparib.
Subject: Ovarian cancer
breast cancer gene (BRCA)
poly(ADP-ribose) polymerase inhibitors (PARP inhibitors)
homologous recombination (HR)
veliparib
talazoparib
OLAPARIB MAINTENANCE THERAPY
ABDOMINAL RADIATION-THERAPY
ADVANCED SOLID MALIGNANCIES
PHASE-I
FALLOPIAN-TUBE
PRIMARY PERITONEAL
VELIPARIB ABT-888
DOSE-ESCALATION
EPITHELIAL OVARIAN
JAPANESE PATIENTS
3122 Cancers
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion


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