Article ; Online: PARP inhibitors: enhancing efficacy through rational combinations.
2023 Volume 129, Issue 6, Page(s) 904–916
Abstract: Poly (ADP-ribose) polymerase inhibitors (PARPi) have significantly changed the treatment landscape for tumours harbouring defects in genes involved in homologous repair (HR) such as BRCA1 and BRCA2. Despite initial responsiveness to PARPi, tumours ... ...
| Abstract | Poly (ADP-ribose) polymerase inhibitors (PARPi) have significantly changed the treatment landscape for tumours harbouring defects in genes involved in homologous repair (HR) such as BRCA1 and BRCA2. Despite initial responsiveness to PARPi, tumours eventually develop resistance through a variety of mechanisms. Rational combination strategies involving PARPi have been explored and are in various stages of clinical development. PARPi combinations have the potential to enhance efficacy through synergistic activity, and also potentially sensitise innately PARPi-resistant tumours to PARPi. Initial combinations involving PARPi with chemotherapy were hindered by significant overlapping haematologic toxicity, but newer combinations with fewer toxicities and more targeted approaches are undergoing evaluation. In this review, we discuss the mechanisms of PARPi resistance and review the rationale and clinical evidence for various PARPi combinations including combinations with chemotherapy, immunotherapy, and targeted therapies. We also highlight emerging PARPi combinations with promising preclinical evidence. |
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| MeSH term(s) | Female ; Humans ; Genes, BRCA2 ; Neoplasms/drug therapy ; Neoplasms/genetics ; Ovarian Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use | |||||
| Chemical Substances | Poly(ADP-ribose) Polymerase Inhibitors | |||||
| Language | English | |||||
| Publishing date | 2023-07-10 | |||||
| Publishing country | England | |||||
| Document type | Journal Article ; Review | |||||
| ZDB-ID | 80075-2 | |||||
| ISSN | 1532-1827 ; 0007-0920 | |||||
| ISSN (online) | 1532-1827 | |||||
| ISSN | 0007-0920 | |||||
| DOI | 10.1038/s41416-023-02326-7 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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