{"entity": "publication", "iuid": "6241cbb9fa3c4d30a33521981edad111", "timestamp": "2026-05-09T17:25:51.874Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/6241cbb9fa3c4d30a33521981edad111.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/6241cbb9fa3c4d30a33521981edad111"}}, "title": "Selective Loss of PARG Restores PARylation and Counteracts PARP Inhibitor-Mediated Synthetic Lethality.", "authors": [{"family": "Gogola", "given": "Ewa", "initials": "E"}, {"family": "Duarte", "given": "Alexandra A", "initials": "AA"}, {"family": "de Ruiter", "given": "Julian R", "initials": "JR"}, {"family": "Wiegant", "given": "Wouter W", "initials": "WW"}, {"family": "Schmid", "given": "Jonas A", "initials": "JA"}, {"family": "de Bruijn", "given": "Roebi", "initials": "R"}, {"family": "James", "given": "Dominic I", "initials": "DI"}, {"family": "Guerrero Llobet", "given": "Sergi", "initials": "S"}, {"family": "Vis", "given": "Daniel J", "initials": "DJ"}, {"family": "Annunziato", "given": "Stefano", "initials": "S"}, {"family": "van den Broek", "given": "Bram", "initials": "B"}, {"family": "Barazas", "given": "Marco", "initials": "M"}, {"family": "Kersbergen", "given": "Ariena", "initials": "A"}, {"family": "van de Ven", "given": "Marieke", "initials": "M"}, {"family": "Tarsounas", "given": "Madalena", "initials": "M"}, {"family": "Ogilvie", "given": "Donald J", "initials": "DJ"}, {"family": "van Vugt", "given": "Marcel", "initials": "M"}, {"family": "Wessels", "given": "Lodewyk F A", "initials": "LFA"}, {"family": "Bartkova", "given": "Jirina", "initials": "J"}, {"family": "Gromova", "given": "Irina", "initials": "I"}, {"family": "And\u00fajar-S\u00e1nchez", "given": "Miguel", "initials": "M"}, {"family": "Bartek", "given": "Jiri", "initials": "J", "orcid": "0000-0003-2013-7525", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/288939950c0c4c6393d35c84e5128b5f.json"}}, {"family": "Lopes", "given": "Massimo", "initials": "M"}, {"family": "van Attikum", "given": "Haico", "initials": "H"}, {"family": "Borst", "given": "Piet", "initials": "P"}, {"family": "Jonkers", "given": "Jos", "initials": "J"}, {"family": "Rottenberg", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2018-06-11", "journal": {"title": "Cancer Cell", "issn": "1878-3686", "volume": "33", "issue": "6", "pages": "1078-1093.e12", "issn-l": "1535-6108"}, "abstract": "Inhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have recently entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, drug resistance is a clinical hurdle, and we poorly understand how cancer cells escape the deadly effects of PARPi without restoring the HR pathway. By combining genetic screens with multi-omics analysis of matched PARPi-sensitive and -resistant Brca2-mutated mouse mammary tumors, we identified loss of PAR glycohydrolase (PARG) as a major resistance mechanism. We also found the presence of PARG-negative clones in a subset of human serous ovarian and triple-negative breast cancers. PARG depletion restores PAR formation and partially rescues PARP1 signaling. Importantly, PARG inactivation exposes vulnerabilities that can be exploited therapeutically.", "doi": "10.1016/j.ccell.2018.05.008", "pmid": "29894693", "labels": {"Affiliated researcher": null}, "xrefs": [{"db": "pii", "key": "S1535-6108(18)30222-8"}], "notes": [], "created": "2019-01-17T13:50:18.200Z", "modified": "2025-11-30T11:19:29.385Z"}