A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles

Biomolecule: a gene-based cancer detection system called tumour-activatable minicircles (TA-MCs). We used it to detect melanoma lung metastases in mice with a sensitive and relatively affordable blood reporter assay. Mice were injected with TA-MCs when tumours reached ~150 mm3. TA-MCs (25 μg/mouse) were complexed with 2.4 μL of linear polyethylenimine to achieve an N/P ratio of 6. This DNA–jetPEI complex was then resuspended in 50 μL 10% (w/v) glucose. Mice were anesthetised with 2% isoflurane then IT injections were performed by injecting the MC-PEI complexes into 4 or 5 loci of each tumour.

Early and accurate detection of cancer is essential to optimising patient outcomes. Of particular importance to prostate cancer is the ability to determine the aggressiveness of a primary tumour, which allows for effective management of patient care. In this work, we propose using gene vectors called tumour-activatable minicircles which deliver an exogenously encoded reporter gene into cancer cells, forcing them to produce a unique and sensitive biomarker. These minicircles express a blood reporter protein called secreted embryonic alkaline phosphatase mediated by the tumour-specific survivin promoter, which exhibits activity graded to prostate cancer aggressiveness. Together, these components underlie a detection system where levels of blood reporter are indicative of not only the presence, but also the metastatic potential of a tumour. Our goal was to assess the ability of tumour-activatable minicircles to detect and characterise primary prostate lesions. Our minicircles produced reporter levels related to survivin expression across a range of prostate cancer cell lines. When survivin-driven minicircles were administered intratumourally into mice, reporter levels in blood samples were significantly higher (p < 0.05) in mice carrying prostate tumours of high versus low-aggressiveness. Continued development of this gene-based system could provide clinicians with a powerful tool to evaluate prostate cancer aggressiveness using a sensitive and affordable blood assay.