Ovarian cancer is the 8th most common cancer in women, accounting for 4.7% of cancer-related deaths worldwide1, and claiming ~1050 Australian lives in 20232. The most common and aggressive subtype, high-grade serous ovarian carcinoma (HGSOC) is characterised by treatment resistance and metastatic disease. Epithelial-to-Mesenchymal-Transition (EMT) is a cellular plasticity program that increases cell motility and is associated with drug resistance3. Unimpeded by anatomical barriers, aggregates of HGSOC cells spread throughout the peritoneal cavity in fluid known as ascites, re-attaching at distal locations, including the omentum. Transforming Growth Factor-β (TGFβ) is a pleiotropic cytokine involved with EMT4. Despite increasing interest in both EMT and TGFβ, there are no clinically-approved therapies targeting these factors in solid tumours. Outcomes of in silico analyses using the virtual ligand-based screening-tool BLAZE™ (Cresset Discovery Services, UK) revealed Topoisomerase II-inhibitor and DNA-damaging agent Teniposide as a potential modulator of TGFβ activity, uncovering a novel role for this drug. Teniposide is FDA-approved for the treatment of refractory childhood Acute Lymphoblastic Leukaemia under the tradename Vumon®. Our preliminary investigations in a physiologically-relevant model of HGSOC cells established using the RASTRUM™ 3D bioprinter (Inventia Life Science), demonstrated that low-doses of Teniposide dismantled cellular aggregates indicative of EMT. This finding provided evidence that Teniposide could be repurposed as an EMT-targeting, anti-invasive agent for HGSOC at low doses, where adjuvant administration with standard-of-care platinum drugs has the potential to increase treatment success. Drug repurposing utilises in silico methods to screen clinically approved drugs with known safety profiles on targets beyond their intended use, bypassing the high costs, extensive timelines, and low success rates of traditional drug discovery pipelines. The repurposing of Teniposide into a low-dose anti-invasive therapy may provide additional treatment options, lengthen progression-free survival, and improve quality of life for patients with HGSOC; a highly-favourable and paradigm-shifting approach.