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Merging new-age biomarkers and nanodiagnostics for precision prostate cancer management

Nature Reviews Urology volume 16, pages 302–317 (2019)Cite this article

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Abstract

The accurate identification and stratified treatment of clinically significant early-stage prostate cancer have been ongoing concerns since the outcomes of large international prostate cancer screening trials were reported. The controversy surrounding clinical and cost benefits of prostate cancer screening has highlighted the lack of strategies for discriminating high-risk disease (that requires early treatment) from low-risk disease (that could be managed using watchful waiting or active surveillance). Advances in molecular subtyping and multiomics nanotechnology-based prostate cancer risk delineation can enable refinement of prostate cancer molecular taxonomy into clinically meaningful and treatable subtypes. Furthermore, the presence of intertumoural and intratumoural heterogeneity in prostate cancer warrants the development of novel nanodiagnostic technologies to identify clinically significant prostate cancer in a rapid, cost-effective and accurate manner. Circulating and urinary next-generation prostate cancer biomarkers for disease molecular subtyping and the newest complementary nanodiagnostic platforms for enhanced biomarker detection are promising tools for precision prostate cancer management. However, challenges in merging both aspects and clinical translation still need to be overcome.

Key points

  • The accurate identification and personalized treatment of high-grade, clinically significant prostate cancer have been ongoing concerns since the outcomes of large international prostate cancer screening trials were published.

  • The combination of next-generation prostate cancer biomarker discoveries and the emergence of companion nanodiagnostic technologies could lead to a new era of precision prostate cancer management.

  • In-depth profiling of prostate cancer has resulted in the discovery of next-generation biomarkers such as TMPRSS2–ETS fusion genes, PCA3 and SCHLAP1, which could improve molecular subtyping and risk stratification.

  • Evolving nanotechnologies such as novel nanomaterials and nanoparticles might benefit clinical translation of next-generation prostate cancer biomarkers by improving detection speed and sensitivity for development of point-of-care diagnostics.

  • Challenges for translating both novel biomarkers and nanotechnology platforms into the clinic still need to be overcome by bridging the gap between clinical and diagnostic disciplines.

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Fig. 1: A potential future of diagnostic miniaturization.
Fig. 2: Miniaturized integrated systems.

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Acknowledgements

K.M.K. acknowledges support from the Australian Government Research Training Program Scholarship and the University of Queensland Graduate School International Travel Award. Although not directly funding this work, K.M.K., P.N.M. and M.T. acknowledge funding from the National Breast Cancer Foundation of Australia (CG 1207), Australian Research Council (DP 140104006 and DP 160102836) and Royal Brisbane Women’s Hospital Foundation (2018 Research Project Grant). These grants have considerably contributed to the environment that stimulates this work. Prostate cancer research in the laboratory of S.A.T. is supported by the US National Institutes of Health, the US Department of Defense and the Prostate Cancer Foundation. S.A.T. is supported by the A. Alfred Taubman Medical Research Institute. The authors thank all patients for their consent, which progresses the research developments mentioned herein.

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Nature Reviews Urology thanks T. van der Kwast and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia

    Kevin M. Koo, Paul N. Mainwaring & Matt Trau

  2. Department of Pathology, Department of Urology, Michigan Centre for Translational Pathology, Comprehensive Cancer Centre, University of Michigan, Ann Arbor, MI, USA

    Scott A. Tomlins

  3. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia

    Matt Trau

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Contributions

K.M.K. researched data for and wrote the manuscript. All authors made substantial contributions to discussion of content and reviewed and edited the manuscript before submission.

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Correspondence to Paul N. Mainwaring, Scott A. Tomlins or Matt Trau.

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Competing interests

The University of Michigan has been issued a patent on ETS gene fusions in prostate cancer on which S.A.T. is a coinventor. The diagnostic field of use has been licensed to Hologic (which acquired Gen-Probe), which has sublicensed rights to Roche (which owns Ventana Medical Systems). S.A.T. has received travel support from, and had a sponsored research agreement with, Compendia Bioscience (which was acquired by Life Technologies, which was acquired by ThermoFisher Scientific). S.A.T. has sponsored research agreements with Astellas and GenomeDx. S.A.T. has served as a consultant for and received honoraria from Roche, Ventana Medical Systems, Almac Diagnostics, Janssen, AbbVie, Sanofi and Astellas (which acquired Medivation). S.A.T. is a cofounder of, consultant for and the Laboratory Director of Strata Oncology. P.N.M. and M.T. are co-founders of XING Technologies, which has licensed intellectual property from the University of Queensland, Australia. P.N.M. is a shareholder of XING Technologies. P.N.M. has served as a consultant, advisory board member and lecturer for and received honoraria, travel support and grant support from Astellas, Bristol-Myers Squibb, Ipsen, Janssen, Medivation, Merck, Novartis, Pfizer and Genentech (a subsidiary of Roche). K.M.K. declares no competing interests.

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Koo, K.M., Mainwaring, P.N., Tomlins, S.A. et al. Merging new-age biomarkers and nanodiagnostics for precision prostate cancer management. Nat Rev Urol 16, 302–317 (2019). https://doi.org/10.1038/s41585-019-0178-2

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