Drug repurposing in oncology: a systematic review of anticancer effects of Lanatoside C at the molecular level.

Cancer continues to pose a major global health burden, with rising incidence and mortality rates. The protracted timelines, and high costs associated with traditional drug development highlight the urgent need for alternative drug development strategies. Drug repurposing, which involves identifying new anticancer uses for existing FDA-approved drugs, offers a promising and cost-effective approach. Lanatoside C, a cardiac glycoside approved for heart conditions, has recently gained attention for its potential anticancer properties. This systematic review consolidates preclinical evidence on the anticancer effects of Lanatoside C, focusing on its molecular mechanisms of action across various cancer types in both in vitro and in vivo models. A systematic search was conducted to identify preclinical studies assessing Lanatoside C’s effects on cancer cell lines and animal models. Studies were included if they evaluated anticancer efficacy and elucidated molecular mechanisms. Data extraction and methodological quality assessment were performed independently by multiple reviewers, using the Toxicological Data Reliability Assessment Tool (ToxRTool). Eighteen studies met inclusion criteria. Lanatoside C consistently inhibited cancer cell proliferation, induced apoptosis, and caused cell cycle arrest (primarily at the G2/M phase) in a dose-dependent manner. Mechanistically, Lanatoside C modulated key signaling pathways, like Wnt/β-catenin, PI3K/AKT/mTOR, MAPK, JAK/STAT, and ER stress/GRP78. Additional mechanisms included ferroptosis induction in lung cancer, and TRAIL-mediated apoptosis in glioblastoma. Both in vitro and in vivo studies demonstrated significant antitumor effects, supporting the translational potential of Lanatoside C as a repurposed anticancer agent. In conclusion, available Preclinical evidence indicates that Lanatoside C exerts broad-spectrum anticancer effects via modulation of different molecular pathways. These findings demonstrate its clinical utility as a monotherapy and in combination regimens, while emphasizing the need for rigorous translational and safety studies to facilitate its integration into oncology practice.