Cargando…

An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions

Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platin...

Descripción completa

Detalles Bibliográficos
Autores principales: Akay, Melek, Funingana, Ionut-Gabriel, Patel, Grisma, Mustapha, Rami, Gjafa, Ernese, Ng, Tony, Ng, Kenrick, Flynn, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593085/
https://www.ncbi.nlm.nih.gov/pubmed/34363200
http://dx.doi.org/10.1007/s40487-021-00167-z
_version_ 1784599636934131712
author Akay, Melek
Funingana, Ionut-Gabriel
Patel, Grisma
Mustapha, Rami
Gjafa, Ernese
Ng, Tony
Ng, Kenrick
Flynn, Michael J.
author_facet Akay, Melek
Funingana, Ionut-Gabriel
Patel, Grisma
Mustapha, Rami
Gjafa, Ernese
Ng, Tony
Ng, Kenrick
Flynn, Michael J.
author_sort Akay, Melek
collection PubMed
description Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit.
format Online
Article
Text
id pubmed-8593085
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Springer Healthcare
record_format MEDLINE/PubMed
spelling pubmed-85930852021-12-02 An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions Akay, Melek Funingana, Ionut-Gabriel Patel, Grisma Mustapha, Rami Gjafa, Ernese Ng, Tony Ng, Kenrick Flynn, Michael J. Oncol Ther Review Niraparib is an oral, potent, highly selective poly-ADP ribose polymerase 1 (PARP1) and PARP2 inhibitor. In most developed countries, it is approved as a maintenance treatment for epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with complete or partial response to platinum-based therapy. These approvals are based on results of randomised, double-blind, placebo-controlled trials, particularly the NOVA trial and more recently the PRIMA trial. In this comprehensive review, we delve into the scientific basis of PARP inhibition, discussing both preclinical and clinical data which have led to the current approval status of niraparib. We also discuss ongoing trials and biological rationale of combination treatments involving niraparib, with particular focus on antiangiogenic drugs, immune checkpoint inhibitors and cyclic GMP-AMP synthase stimulator of interferon genes (cGAS/STING) pathway. In addition, we reflect on potential strategies and challenges of utilising current biomarkers for treatment selection of patients to ensure maximal benefit. Springer Healthcare 2021-08-07 /pmc/articles/PMC8593085/ /pubmed/34363200 http://dx.doi.org/10.1007/s40487-021-00167-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Review
Akay, Melek
Funingana, Ionut-Gabriel
Patel, Grisma
Mustapha, Rami
Gjafa, Ernese
Ng, Tony
Ng, Kenrick
Flynn, Michael J.
An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title_full An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title_fullStr An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title_full_unstemmed An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title_short An In-Depth Review of Niraparib in Ovarian Cancer: Mechanism of Action, Clinical Efficacy and Future Directions
title_sort in-depth review of niraparib in ovarian cancer: mechanism of action, clinical efficacy and future directions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593085/
https://www.ncbi.nlm.nih.gov/pubmed/34363200
http://dx.doi.org/10.1007/s40487-021-00167-z
work_keys_str_mv AT akaymelek anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT funinganaionutgabriel anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT patelgrisma anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT mustapharami anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT gjafaernese anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT ngtony anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT ngkenrick anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT flynnmichaelj anindepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT akaymelek indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT funinganaionutgabriel indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT patelgrisma indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT mustapharami indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT gjafaernese indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT ngtony indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT ngkenrick indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections
AT flynnmichaelj indepthreviewofniraparibinovariancancermechanismofactionclinicalefficacyandfuturedirections