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dc.contributor.authorAbbotts, Rachel
dc.contributor.authorDellomo, Anna J
dc.contributor.authorRassool, Feyruz V
dc.date.accessioned2022-06-13T13:26:54Z
dc.date.available2022-06-13T13:26:54Z
dc.date.issued2022-05-26
dc.identifier.urihttp://hdl.handle.net/10713/19122
dc.description.abstractThe poly(ADP-ribose) polymerase (PARP) family of proteins has been implicated in numerous cellular processes, including DNA repair, translation, transcription, telomere maintenance, and chromatin remodeling. Best characterized is PARP1, which plays a central role in the repair of single strand DNA damage, thus prompting the development of small molecule PARP inhibitors (PARPi) with the intent of potentiating the genotoxic effects of DNA damaging agents such as chemo- and radiotherapy. However, preclinical studies rapidly uncovered tumor-specific cytotoxicity of PARPi in a subset of cancers carrying mutations in the BReast CAncer 1 and 2 genes (BRCA1/2), which are defective in the homologous recombination (HR) DNA repair pathway, and several PARPi are now FDA-approved for single agent treatment in BRCA-mutated tumors. This phenomenon, termed synthetic lethality, has now been demonstrated in tumors harboring a number of repair gene mutations that produce a BRCA-like impairment of HR (also known as a 'BRCAness' phenotype). However, BRCA mutations or BRCAness is present in only a small subset of cancers, limiting PARPi therapeutic utility. Fortunately, it is now increasingly recognized that many small molecule agents, targeting a variety of molecular pathways, can induce therapeutic BRCAness as a downstream effect of activity. This review will discuss the potential for targeting a broad range of molecular pathways to therapeutically induce BRCAness and PARPi synthetic lethality.en_US
dc.description.urihttps://doi.org/10.3390/cancers14112640en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancersen_US
dc.subjectBRCA mutationsen_US
dc.subjectBRCAnessen_US
dc.subjectDNA repairen_US
dc.subjectPARP inhibitoren_US
dc.subjectcell cycle inhibitoren_US
dc.subjectepigenetic therapyen_US
dc.subjecthomologous recombinationen_US
dc.subjectkinase inhibitoren_US
dc.subjectsynthetic lethalityen_US
dc.titlePharmacologic Induction of BRCAness in -Proficient Cancers: Expanding PARP Inhibitor Use.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/cancers14112640
dc.identifier.pmid35681619
dc.source.journaltitleCancers
dc.source.volume14
dc.source.issue11
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countrySwitzerland


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