Merging New-Age Biomarkers and Nanodiagnostics for Precision Prostate Cancer Management

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 [European Randomized Study of Screening for Prostate Cancer (ERSPC) trial and Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO)] trials were published. However, accurate identification and treatment of high-grade aggressive prostate cancer remains a challenging and controversial conundrum in oncology. A single biomarker is unlikely to be sufficient to achieve the required diagnostic sensitivity and specificity to enable accurate prostate cancer risk stratification. In-depth profiling of prostate cancer has resulted in the discovery of next-generation biomarkers such as, which could improve molecular subtyping and risk stratification. Emerging evidence using such various next-generation prostate cancer biomarkers shows that effective prostate cancer classification into different molecular subtypes is potentially amenable for precision treatment strategies. Additionally, 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.

In this review¹, we discussed the progress of biomarker-driven prostate cancer molecular subtyping and the development of companion nanodiagnostic strategies to refine clinical biomarker detection. We also discussed the existing challenges of merging both aspects for precision prostate cancer management and provide insights into possible solutions.

We first covered novel prostate cancer-specific biomarkers (TMPRSS2–ETS fusion genes, PCA3, SChLAP1, PTEN, AR-V7) in blood and urine with better disease-informing abilities than PSA, as well as several existing biomarker-based diagnostic assays for supporting PSA screening outcomes that are available to clinicians. We then reviewed the emergence of nanotechnology-based approaches for miniaturized prostate cancer screening; including nanostructured materials, nanoparticles, and miniaturized integrated systems (Fig. 1). Lastly, we examined the current challenges in clinical translation of combined cutting-edge PCa biomarkers and nanodiagnostics: i) Validation of biomarker panels, ii) Clinical verification of nanodiagnostics, iii) Acceleration of validation processes, iv) Standardization of protocols, and v) Multidisciplinary collaboration.

All in all, we hope this Review bridges the knowledge gap between the prostate cancer clinical and nanodiagnostic research fields by informing clinicians about future possibilities and benefits of prostate cancer nanotechnology-based screening, and alerting nanotechnology researchers to the availability of next- generation prostate cancer biomarkers for integration into their nanodiagnostic research.

Merging New-Age Biomarkers and Nanodiagnostics .png

Fig. 1 Miniaturized integrated systems that miniaturize and integrate an entire laboratory-based biomarker analysis workflow. (a) Lab-on-a-chip. (b) Lab-in-a-drop². Figure adapted from Nature Springer.

Written by:
Kevin M. Koo¹, Paul N. Mainwaring^1*, Scott A. Tomlins^2* and Matt Trau^{1, 3*}
¹Centre for Personalized Nanomedicine, Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia
²Department of Pathology, Department of Urology, Michigan Centre for Translational Pathology, Comprehensive Cancer Centre, University of Michigan, Ann Arbor, MI, USA
³School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Australia

References

Koo, K. M.; Mainwaring, P. N.; Tomlins, S. A. & Trau, M. (2019) Merging new-age biomarkers and nanodiagnostic platforms for precision prostate cancer management. Rev. Urol. https://doi.org/10.1038/s41585-019-0178-2
Koo, K. M.; Wee, E. J. H.; Wang, Y. & Trau, M. (2017) Enabling miniaturised personalised diagnostics: from lab- on-a-chip to lab- in-a- drop. Chip 17, 3200–3220.

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