University of Oulu

Boussios S, Moschetta M, Karihtala P, Samartzis EP, Sheriff M, Pappas-Gogos G, Ozturk MA, Uccello M, Karathanasi A, Tringos M, Rassy E, Pavlidis N. Development of new poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis? Ann Transl Med 2020;8(24):1706. doi: 10.21037/atm.2020.03.156

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

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Author: Boussios, Stergios1,2; Moschetta, Michele3; Karihtala, Peeter4,5;
Organizations: 1Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, Kent, UK
2AELIA Organization, 9th Km Thessaloniki-Thermi, Thessaloniki, Greece
3Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
4Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
5Department of Oncology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
6Department of Gynecology and Gynecological Cancer Center, University Hospital Zurich, Zurich, Switzerland
7Department of Urology, Medway NHS Foundation Trust, Gillingham, Kent, UK
8Department of Surgery, University Hospital of Ioannina, Ioannina, Greece
9Department of Internal Medicine, Bahcesehir University School of Medicine, Istanbul, Turkey
10Northampton General Hospital NHS Trust, Cliftonville, Northampton, UK
11School of Psychology, Aristotle University of Thessaloniki, Thessaloniki, Greece
12Department of Cancer Medicine, Gustave Roussy Institut, Villejuif, France
13Department of Hematology-Oncology, Hotel Dieu de France University Hospital, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
14Medical School, University of Ioannina, Ioannina, Greece
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe202103117182
Language: English
Published: AME Publishing Company, 2020
Publish Date: 2021-03-11
Description:

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.

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Series: Annals of translational medicine
ISSN: 2305-5839
ISSN-E: 2305-5847
ISSN-L: 2305-5839
Volume: 8
Issue: 24
Article number: 1706
DOI: 10.21037/atm.2020.03.156
OADOI: https://oadoi.org/10.21037/atm.2020.03.156
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3123 Gynaecology and paediatrics
3122 Cancers
Subjects:
Funding: The authors acknowledge support from the Research and Innovation department of Medway NHS Foundation Trust.
Copyright information: © Annals of Translational Medicine. All rights reserved. This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
  https://creativecommons.org/licenses/by-nc-nd/4.0/