Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer
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Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada
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Faculty of Medicine, Université de Montréal, Montréal, QC H3C 3T5, Canada
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Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), l’Institut de Cancer de Montreal, Montreal, QC H2X 0A9, Canada
4
Division of Surgical Oncology, Department of Surgery, Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, QC H2X 0C1, Canada
*
Author to whom correspondence should be addressed.
Academic Editors: Maryam Nakhjavani and Amanda Townsend
Pharmaceuticals 2021, 14(12), 1270; https://doi.org/10.3390/ph14121270
Received: 8 November 2021
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Revised: 27 November 2021
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Accepted: 29 November 2021
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Published: 6 December 2021
(This article belongs to the Special Issue Potential Molecular Targets and Therapeutics in Triple-Negative Breast Cancer)
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and is known to be associated with a poor prognosis and limited therapeutic options. Poly (ADP-ribose) polymerase inhibitors (PARPi) are targeted therapeutics that have demonstrated efficacy as monotherapy in metastatic BRCA-mutant (BRCAMUT) TNBC patients. Improved efficacy of PARPi has been demonstrated in BRCAMUT breast cancer patients who have either received fewer lines of chemotherapy or in chemotherapy-naïve patients in the metastatic, adjuvant, and neoadjuvant settings. Moreover, recent trials in smaller cohorts have identified anti-tumor activity of PARPi in TNBC patients, regardless of BRCA-mutation status. While there have been concerns regarding the efficacy and toxicity of the use of PARPi in combination with chemotherapy, these challenges can be mitigated with careful attention to PARPi dosing strategies. To better identify a patient subpopulation that will best respond to PARPi, several genomic biomarkers of homologous recombination deficiency have been tested. However, gene expression signatures associated with PARPi response can integrate different pathways in addition to homologous recombination deficiency and can be implemented in the clinic more readily. Taken together, PARPi have great potential for use in TNBC patients beyond BRCAMUT status, both as a single-agent and in combination.
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Keywords:
triple-negative breast cancer; PARP inhibitors; combination therapy; predictive biomarkers
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MDPI and ACS Style
Yordanova, M.; Hubert, A.; Hassan, S. Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer. Pharmaceuticals 2021, 14, 1270. https://doi.org/10.3390/ph14121270
AMA Style
Yordanova M, Hubert A, Hassan S. Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer. Pharmaceuticals. 2021; 14(12):1270. https://doi.org/10.3390/ph14121270
Chicago/Turabian StyleYordanova, Mariya, Audrey Hubert, and Saima Hassan. 2021. "Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer" Pharmaceuticals 14, no. 12: 1270. https://doi.org/10.3390/ph14121270
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