Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches
Abstract
:Simple Summary
Abstract
1. Introduction
2. Mutations in BRCA 1/2 Genes
3. Poly (ADP-Ribose) Polymerase 1 (PARP1) Is Critical for the Survival of BRCA-Mutated Cells
4. PARPi Induces Synthetic Lethality in BRCA-Mutated Cells
5. Resistance to PARPi
6. Molecular Mechanisms for Resistance to PARPi
6.1. Dysregulated Molecular Signaling
6.2. Reverse Mutations
6.3. Restoration of Replication Fork Stability
6.4. Effect of the Increased Drug Efflux
7. Approaches to Enhance the Effects of the PARPi Treatment
7.1. PARPi and Chemotherapy
7.2. PARPi and Immune Checkpoint Inhibitors
7.3. PARPi and ATR/Chk1/Wee1-Inhibitor Therapy
7.4. PARPi and BRD4/BET Inhibitor Therapy
7.5. PARPi and CDK12 Inhibitor Therapy
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Dilmac, S.; Ozpolat, B. Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches. Cancers 2023, 15, 3642. https://doi.org/10.3390/cancers15143642
Dilmac S, Ozpolat B. Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches. Cancers. 2023; 15(14):3642. https://doi.org/10.3390/cancers15143642
Chicago/Turabian StyleDilmac, Sayra, and Bulent Ozpolat. 2023. "Mechanisms of PARP-Inhibitor-Resistance in BRCA-Mutated Breast Cancer and New Therapeutic Approaches" Cancers 15, no. 14: 3642. https://doi.org/10.3390/cancers15143642