{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:59:54Z","timestamp":1785160794900,"version":"3.55.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"6","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","award":["02NUK032,02NUK035B,02NUK076E"],"award-info":[{"award-number":["02NUK032,02NUK035B,02NUK076E"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["INST 337\/15-1,INST 337\/16-1,INST 152\/837-1,INST 152\/947-1 FUGG"],"award-info":[{"award-number":["INST 337\/15-1,INST 337\/16-1,INST 152\/837-1,INST 152\/947-1 FUGG"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,16]]},"abstract":"<jats:p>\n                    Radiotherapy (RT) is a central treatment for prostate cancer (PCa), relying on the induction of DNA double-strand breaks (DSBs). Tumor ability to repair these breaks limits RT efficacy, making DSB repair inhibitors potential radiosensitizers. However, many of these inhibitors lack tumor specificity and harm normal cells. Therefore, tumor-specific radiosensitization strategies are critically needed for PCa. Approximately 50% of PCa cases harbor the TMPRSS2-ERG gene fusion, leading to overexpression of the ERG transcription factor (ERG\n                    <jats:sup>+<\/jats:sup>\n                    ). In this study, we demonstrate that ERG\n                    <jats:sup>+<\/jats:sup>\n                    tumors shift DSB repair toward the poly(ADP-ribose) polymerase 1\u2013dependent end-joining (PARP1-EJ) pathway. Proteomic and Western blot analyses revealed elevated PARP1, XRCC1, and LIG3 levels in ERG\n                    <jats:sup>+<\/jats:sup>\n                    cells. Notably, PARP inhibition with olaparib increased residual \u03b3H2AX\/53BP1 foci postirradiation in ERG\n                    <jats:sup>+<\/jats:sup>\n                    cells, indicating enhanced radiosensitization. In tissue slice cultures (TSCs) from 53 tumors of patients with high-risk PCa, olaparib selectively increased \u03b3H2AX\/53BP1 foci selectively in ERG\n                    <jats:sup>+<\/jats:sup>\n                    samples. ERG\n                    <jats:sup>+<\/jats:sup>\n                    patient\u2013derived organoids also showed significantly delayed growth when treated with olaparib plus RT, compared with either treatment alone. Interestingly, ERG-negative cells within ERG\n                    <jats:sup>+<\/jats:sup>\n                    TSCs were similarly radiosensitized by olaparib, likely through bystander effect, with residual 53BP1 foci levels comparable to those in ERG\n                    <jats:sup>+<\/jats:sup>\n                    cells. This was confirmed by medium exchange experiments. These findings suggest that ERG expression promotes dependency on the PARP1-EJ pathway, rendering ERG\n                    <jats:sup>+<\/jats:sup>\n                    PCa more susceptible to PARP inhibition. This supports combining PARP inhibitors with RT for tumor-selective radiosensitization in ERG\n                    <jats:sup>+<\/jats:sup>\n                    patients.\n                  <\/jats:p>","DOI":"10.1172\/jci194949","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T17:00:33Z","timestamp":1770138033000},"source":"Crossref","is-referenced-by-count":5,"title":["Overexpression of the ERG oncogene in prostate cancer identifies candidates for PARP inhibitor\u2013based radiosensitization"],"prefix":"10.1172","volume":"136","author":[{"given":"Sabrina","family":"K\u00f6cher","sequence":"first","affiliation":[{"name":"Department of Radiotherapy and Radiooncology and"},{"name":"Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed E.","family":"Elsesy","sequence":"additional","affiliation":[{"name":"Department of 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