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
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Publish Date: | 2021-03-11 |
Description: |
AbstractEpithelial 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. see all
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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/ |