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

Gene Therapy volume 26, pages 177–186 (2019)Cite this article

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Abstract

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.

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Acknowledgements

We thank Dr. Amanda Hamilton and Gurkamal Doel for their assistance on aspects of the investigation. This work was in part funded by Canada Graduate Master’s Scholarship from the National Science and Engineering Research Council of Canada (TW). This work was also funded by a Movember Discovery Grant from Prostate Cancer Canada (JAR) and the Petro Canada Young Innovator Award from Western University (JAR).

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  1. These authors contributed equally: TianDuo Wang, Yuanxin Chen

Authors and Affiliations

  1. Robarts Research Institute–Imaging Laboratories, University of Western Ontario, London, ON, Canada

    TianDuo Wang, Yuanxin Chen & John. A. Ronald

  2. Department of Medical Biophysics, University of Western Ontario, London, ON, Canada

    TianDuo Wang & John. A. Ronald

  3. Lawson Health Research Institute, London, ON, Canada

    John. A. Ronald

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  1. TianDuo Wang
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Correspondence to John. A. Ronald.

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Conflict of interest

JAR is co-inventor on a US patent called “Tumour-specific minicircles for cancer screening” (Patent number 9534248; 2017/1/3), which describes the invention of tumour-activatable minicircles for cancer detection. This patent has been licensed by the start-up company Earli, Inc., and JAR holds shares and is a consultant of this company. The remaining authors declare that they have no conflict of interest.

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Wang, T., Chen, Y. & Ronald, J.A. A novel approach for assessment of prostate cancer aggressiveness using survivin-driven tumour-activatable minicircles. Gene Ther 26, 177–186 (2019). https://doi.org/10.1038/s41434-019-0067-6

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