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However, tumors treated with PARPi eventually relapse despite initial responsiveness. In this study, it is demonstrated that the anti\u2010angiogenic agent lenvatinib synergizes effectively with PARPi, resulting in substantial tumor regression and significantly extended survival. Genomic analysis of tumors reveals that PARPi induces widespread transcriptomic changes that are predominantly pro\u2010inflammatory, thereby promoting tumor angiogenesis. Prickle4, a planar cell polarity protein, is identified as a critical mediator of PARPi\u2010induced neovascularization. Targeting Prickle4 effectively overcomes PARPi resistance in these tumors. Collectively, these findings identified the Prickle4\u2010mediated microenvironmental remodeling as the key resistance mechanism to PARPi, and support the therapeutic promise of multimodal therapy combining PARPi with anti\u2010angiogenic agents for glioma treatment.<\/jats:p>","DOI":"10.1002\/advs.202503866","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T14:25:37Z","timestamp":1763130337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prickle4 Drives Microenvironmental Remodeling and Resistance to Parp Inhibition in IDH\u2010Mutant Glioma"],"prefix":"10.1002","volume":"13","author":[{"given":"Ju","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pathology School of Basic Medical Sciences Shanghai Fifth People's Hospital Fudan University  Shanghai 200040 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