Drug repurposing of ticagrelor suppresses renal cell carcinoma growth by blockading the EGFR/PI3K/AKT axis.

BACKGROUND: Renal cell carcinoma (RCC) remains one of the most prevalent urological malignancies. Although targeted therapies have expanded therapeutic options, a substantial proportion of patients still experience poor outcomes, underscoring the need for more effective and less toxic strategies. Ticagrelor, a novel antiplatelet agent, has recently shown antineoplastic potential in several cancers; however, its role and mechanism in RCC remain undefined. METHODS: In vitro effects of ticagrelor on RCC cells were evaluated using CCK-8, EdU, and AO/PI assays for proliferation/apoptosis, wound healing and Transwell assays for migration/invasion. In vivo efficacy was assessed in an RCC cell-derived xenograft (CDX) model. Network pharmacology and Western blotting were employed to elucidate the underlying mechanism. RESULTS: Ticagrelor suppressed proliferation, migration, invasion and adhesion, and promoted apoptosis in RCC cells. In CDX mice, tumor growth was significantly inhibited. Mechanistically, the EGFR/PI3K/AKT pathway was identified as the key mediator of ticagrelor's antitumor activity in RCC. CONCLUSIONS: Ticagrelor exerts anti-RCC effects via blockade of the EGFR/PI3K/AKT signaling axis, highlighting its translational potential and positioning this pathway as a therapeutic target and possible biomarker in RCC.