Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Feb;26(2):103-113.
doi: 10.1007/s11912-023-01488-0. Epub 2024 Jan 2.

PARP Inhibitors in Breast Cancer: a Short Communication

Gordon R Daly #  1   2 , Maen Monketh AlRawashdeh #  3   4 , Jason McGrath #  3 , Gavin P Dowling  3   4 , Luke Cox  3 , Sindhuja Naidoo  3   4 , Damir Vareslija  3 , Arnold D K Hill  3   4 , Leonie Young  3
Affiliations
Review

PARP Inhibitors in Breast Cancer: a Short Communication

Gordon R Daly et al. Curr Oncol Rep. 2024 Feb.

Abstract

Purpose of review: In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in the treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss the current uses, limitations, and future directions for PARP inhibitors (PARPis) in the treatment of breast cancer.

Recent findings: Following the results of the OlympiAD and EMBRACA trials, PARPis were approved in HER2-negative breast cancer with a germline BRCA mutation. We reviewed this class of drugs' mechanism of action, efficacy, and limitations, as well as further studies that discussed resistance, impaired homologous recombination repair (HRR), and the combination of PARPis with other drugs. Improving understanding of HRR, increasing the ability to target resistance, and combining PARPis with other novel agents are continuing to increase the clinical utility of PARPis.

Keywords: BRCA; Breast cancer; Homologous repair deficiency; PARP inhibitor.

PubMed Disclaimer

Conflict of interest statement

Grant awarded to the author Prof. Leonie Young by Breast Cancer Now as PI to the Royal College of Surgeons in Ireland to investigate the efficacy of PARP inhibitors to treat breast cancer brain metastasis. There are no other competing interests to be disclosed.

Figures

Fig. 1
Fig. 1
A summary of PARP inhibitor’s mechanism of action. On the top is a PARP inhibitor leading to cell death by trapping PARP1 to DNA causing DNA damage and cell death. On the bottom is the classical synthetic lethality concept, where the PARP inhibitor blocks the cell’s ability to repair single strand breaks using the base excision repair pathway, causing it to transform into a double stranded break that cannot be repaired in cells with HRD. Created with https://www.biorender.com/
Fig. 2
Fig. 2
Common mechanisms behind PARP inhibitor resistance. A ABCB1 transporter overexpression leads to increased drug efflux. B PARP1 trapping is one of the mechanisms PARP inhibitors cause damage to cells; decreased PARP trapping, therefore, is a cause of resistance. C Restoration of HRR leads to tumor cells being able to repair the double-strand breaks caused by the PARP inhibitor. D Increased replication fork stability, for example, due to decrease in PTIP or EZH2, leads to increased cell survival and resistance to PARP inhibitors. Created with https://www.biorender.com/
See this image and copyright information in PMC

References

    1. Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95(1130):20211033. doi: 10.1259/bjr.20211033. - DOI - PMC - PubMed
    1. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389(10074):1134–1150. doi: 10.1016/S0140-6736(16)31891-8. - DOI - PubMed
    1. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288–300. doi: 10.1001/jama.2018.19323. - DOI - PubMed
    1. American Cancer Society . Cancer facts & figures 2022. Atlanta: American Cancer Society; 2022.
    1. Cortesi L, Rugo HS, Jackisch C. An overview of PARP inhibitors for the treatment of breast cancer. Target Oncol. 2021;16(3):255–282. doi: 10.1007/s11523-021-00796-4. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances