{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:40:33Z","timestamp":1792093233340,"version":"4.4.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["EMBO Mol Med"],"published-print":{"date-parts":[[2023,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Personalised oncology is at the forefront of cancer research. The goal of personalised oncology is to selectively kill cancer cells while minimising side effects on normal tissue. This can be achieved by identifying and targeting cancer vulnerabilities that distinguish it from normal cells. Many cancers are deficient in high\u2010fidelity DNA repair pathways that maintain genomic stability, such as homologous recombination (HR). Such cancers are highly sensitive to targeted therapies that induce DNA damage or inhibit DNA repair pathways. A notable example and a poster child of personalised oncology are PARP1\/2 inhibitors (PARPi) that selectively kill HR\u2010deficient (HRD) cancer cells by preventing repair of DNA gaps or single\u2010strand breaks (SSBs) (Slade, 2020). Inhibitors of cell cycle checkpoints such as CHK1 and WEE1 can also eliminate HRD cancers by pushing cancer cells through the cell cycle despite unrepaired DNA damage and causing death by mitotic catastrophe (Groelly\n                    <jats:italic>et\u00a0al<\/jats:italic>\n                    , 2022). PARPi have been approved for the treatment of ovarian, breast, pancreatic, and prostate cancer but other cancer types with an HRD signature (HRD\n                    <jats:italic>ness<\/jats:italic>\n                    ) may also respond to PARPi treatment. Planas\u2010Paz\n                    <jats:italic>et\u00a0al<\/jats:italic>\n                    (2023) now show that many sarcomas show HRD\n                    <jats:italic>ness<\/jats:italic>\n                    and respond to PARP1\/2 and WEE1 inhibitors, thus offering a new personalised oncology approach for this treatment\u2010refractory cancer.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202317453","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T07:10:30Z","timestamp":1679037030000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Leveraging homologous recombination repair deficiency in sarcoma"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-5910","authenticated-orcid":false,"given":"Dea","family":"Slade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-0424","authenticated-orcid":false,"given":"Joanna I","family":"Loizou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"BFEMMM202317453_CR1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41571-021-00532-x","volume":"18","author":"MP Dias","year":"2021","unstructured":"Dias MP, Moser SC, Ganesan S, Jonkers J (2021) Understanding and overcoming resistance to PARP inhibitors in cancer therapy. Nat Rev Clin Oncol 18: 773\u2013791","journal-title":"Nat Rev Clin Oncol"},{"key":"BFEMMM202317453_CR2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.5306\/wjco.v11.i4.180","volume":"11","author":"J G\u00f3mez","year":"2020","unstructured":"G\u00f3mez J, Tsagozis P (2020) Multidisciplinary treatment of soft tissue sarcomas: an update. World J Clin Oncol 11: 180\u2013189","journal-title":"World J Clin Oncol"},{"key":"BFEMMM202317453_CR3","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41568-022-00535-5","volume":"23","author":"FJ Groelly","year":"2022","unstructured":"Groelly FJ, Fawkes M, Dagg RA, Blackford AN, Tarsounas M (2022) Targeting DNA damage response pathways in cancer. 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Theranostics 10: 9477\u20139494","journal-title":"Theranostics"},{"key":"BFEMMM202317453_CR6","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1038\/s41467-020-19406-4","volume":"11","author":"L Nguyen","year":"2020","unstructured":"Nguyen L, W M Martens J, Van Hoeck A, Cuppen E (2020) Pan\u2010cancer landscape of homologous recombination deficiency. Nat Commun 11: 5584","journal-title":"Nat Commun"},{"key":"BFEMMM202317453_CR7","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202216863","volume":"15","author":"L Planas\u2010Paz","year":"2023","unstructured":"Planas\u2010Paz L, Pliego\u2010Mendieta A, Hagedorn C, Aguilera\u2010Garcia D, Haberecker M, Arnold F, Herzog M, Bankel L, Guggenberger R, Steiner S et\u00a0al (2023) Unravelling homologous recombination repair deficiency\u00a0and therapeutic opportunities in soft tissue and bone sarcoma. EMBO Mol Med 15: e16863","journal-title":"EMBO Mol Med"},{"key":"BFEMMM202317453_CR8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.trecan.2020.09.007","volume":"7","author":"A Schrempf","year":"2021","unstructured":"Schrempf A, Slyskova J, Loizou JI (2021) Targeting the DNA repair enzyme polymerase \u03b8 in cancer therapy. Trends Cancer 7: 98\u2013111","journal-title":"Trends Cancer"},{"key":"BFEMMM202317453_CR9","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1634\/theoncologist.2018-0448","volume":"24","author":"ND Seligson","year":"2019","unstructured":"Seligson ND, Kautto EA, Passen EN, Stets C, Toland AE, Millis SZ, Meyer CF, Hays JL, Chen JL (2019) BRCA1\/2 functional loss defines a targetable subset in Leiomyosarcoma. Oncologist 24: 973\u2013979","journal-title":"Oncologist"},{"key":"BFEMMM202317453_CR10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1101\/gad.334516.119","volume":"34","author":"D Slade","year":"2020","unstructured":"Slade D (2020) PARP and PARG inhibitors in cancer treatment. 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