MP07-20 DEVELOPMENT AND VALIDATION OF GENOMIC SIGNATURE THAT PREDICTS ADT TREATMENT FAILURE

prostate cancer. Whilst it provides cancer specific survival advantage in those with metastatic disease and those undergoing radiotherapy for intermediate to high risk localized prostate cancer, it is associated with significant metabolic adverse effects. ADMET (ADT and metformin) trial was set up to determine whether adjuvant metformin would reverse metabolic syndrome induced by ADT, and whether molecular changes in CTCs could be detected during the treatment. METHODS: We established a multi-centre randomized, placebo controlled clinical trial. In total, 80 patients with metastatic prostate cancer who are commenced on ADT are expected to be recruited and reviewed 6 weekly for 42 weeks. Forty seven patients have so far been screened as a part of the trial. 5ml of whole blood was collected from patients for CTC enrichment, enumeration and propagation. Enrichment was performed using CD45 negative selection kit (RosetteSep). CTCs were identified using immunofluorescence imaging with antibodies against prostate specific antigen, cytokeratin, CD45 and nucleus. Cells were propagated in customized stem cell solution with hypoxic conditions (8%). RESULTS: At screening, 39 of 47 patients demonstrated circulating tumour cells with the mean number of 847 (range 1-4750, SD+/-1731). In 32 of 39 samples, the enriched samples could be propagated temporarily with the peak population being reached at 7-20 days. Cells were cultured in both 2D and 3D conditions and temporary organoids could be developed from 12 patients. Cultured cells were then prepared for RNA extraction, with the ultimate aim of being able to propagate enough samples for RNA sequencing. With the ability to further culture the harvested CTCs, we were able to observe the cells under the influence of numerous prostate cancer treatment medications using Incucyte, demonstrating the potential for personalized medicine. In 26 patients, who were available for longitudinal follow up, all patients demonstrated persistence of CTCs. CONCLUSIONS: Circulating tumour cell technology remains a viable option as a means of providing biomarker information and tumour activity indicator in delivering precision medicine. Firstly, enumeration can be used to help determine the response to a treatment. Secondly, temporary culture and progression into development of organoids may be used to allow for downstream analysis and therapeutic decision.