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Although PTEN loss, a frequent alteration in EC, has been implicated in impaired homologous recombination and increased sensitivity to PARP inhibitors, responses to PARP inhibitor monotherapy remain variable and are often limited by resistance mechanisms in PTEN\u2010deficient tumours. Here, we show that the dual PARP\/tankyrase (TNKS) inhibitor JPI\u2010547 exerts potent antitumor activity, particularly in PTEN\u2010deficient Ishikawa tumours. In\u00a0vitro, JPI\u2010547 and olaparib more effectively reduced cell survival in PTEN\u2010deficient cells, and combined treatment with olaparib and the TNKS inhibitor XAV\u2010939 induced synergistic cytotoxicity with elevated DNA double\u2010strand breaks. Dual PARP\/TNKS inhibition did not further suppress RAD51 but modulated non\u2010homologous end joining and attenuated Wnt\/\u03b2\u2010catenin signalling in a PTEN\u2010dependent manner. PTEN knockdown further showed enhanced vulnerability to combined targeting. These findings show that JPI\u2010547 enhances antitumor efficacy in PTEN\u2010deficient EC by disrupting DNA repair pathways and Wnt signalling, supporting dual PARP\/TNKS inhibition as a potential therapeutic strategy and providing a rationale for further clinical evaluation.<\/jats:p>","DOI":"10.1111\/jcmm.71242","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T03:59:43Z","timestamp":1781323183000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual\n                    <scp>PARP<\/scp>\n                    \/Tankyrase Inhibition Enhances Antitumor Efficacy in\n                    <scp>PTEN<\/scp>\n                    \u2010Deficient Endometrial Cancer"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-8311","authenticated-orcid":false,"given":"Sung Wan","family":"Kang","sequence":"first","affiliation":[{"name":"Department of 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