Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Patented prostate cancer biomarkers

Nature Reviews Urology volume 9, pages 464–472 (2012)Cite this article

Subjects

Abstract

Prostate cancer is the most frequently diagnosed cancer in men. However, current diagnostic techniques (including serum PSA level measurement) lack sufficient specificity and sensitivity to determine the aggressiveness of the disease and to identify appropriate treatment. Additional reliable biomarkers are needed that can facilitate early diagnosis of prostate cancer, determine the patient's prognosis and predict responses to a given therapeutic intervention. To achieve clinical utility, biomarkers require the potential for commercialization, and such an investment is generally only made if a financial return is promised. Patenting is one way to protect the intellectual property surrounding such biomarkers and several patented biomarkers are being developed, although few have been validated in large-scale clinical trials.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther. 69, 89–95 (2001).

  2. Shariat, S. F. et al. Tumour markers in prostate cancer I: blood based markers. Acta. Oncol. 50 (Suppl. 1), 61–75 (2011).

    Article  Google Scholar 

  3. Jackson, T. et al. Disclosure of diagnosis and treatment among early stage prostate cancer survivors. Patient Educ. Couns. 79, 239–244 (2010).

    Article  Google Scholar 

  4. Cancer Facts & Figures 2009. American Cancer Society [online], (2009).

  5. Lukes, M. et al. Prostate-specific antigen: current status. Folia Biol. (Praha) 47, 41–49 (2001).

    CAS  Google Scholar 

  6. Allhoff, E., de Riese, W., Eifinger, M., Pethke, J. & Jones, U. Prostate-specific antigen-comparative clinical appreciation of a serodiagnostic measure after 8 years of experience. World J. Urol. 7, 12–16 (1989).

    Article  Google Scholar 

  7. Cooner, W. H. et al. Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J. Urol. 143, 1146–1154 (1990).

    Article  CAS  Google Scholar 

  8. Aly, M., Wiklund, F. & Grönberg, H. Early detection of prostate cancer with emphasis on genetic markers 1. Acta. Oncol. 50 (Suppl. 1), 18–23 (2011).

    Article  CAS  Google Scholar 

  9. Wright, J. L. & Lange, P. H. Newer potential biomarkers in prostate cancer. Rev. Urol. 9, 207–213 (2007).

    PubMed  PubMed Central  Google Scholar 

  10. Thorpe, A. & Neal, D. Benign prostatic hyperplasia. Lancet 361, 1359–1367 (2003).

    Article  CAS  Google Scholar 

  11. De Nunzio, C. et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur. Urol. 60, 106–117 (2011).

    Article  CAS  Google Scholar 

  12. Gulati, R. et al. What if I don't treat my PSA-detected prostate cancer? Answers from three natural history models. Cancer Epidemiol. Biomarkers Prev. 20, 740–750 (2011).

    Article  Google Scholar 

  13. Auprich, M. et al. Contemporary role of prostate cancer antigen 3 in the management of prostate cancer. Eur. Urol. 60, 1045–1054 (2011).

    Article  CAS  Google Scholar 

  14. Auprich, M. et al. Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging. Eur. Urol. 59, 96–105 (2011).

    Article  Google Scholar 

  15. Oon, S. F., Pennington, S. R., Fitzpatrick, J. M. & Watson, R. W. Biomarker research in prostate cancer—towards utility, not futility. Nat. Rev. Urol. 8, 131–138 (2011).

    Article  CAS  Google Scholar 

  16. Chodak, G. W., Keller, P. & Schoenberg, H. W. Assessment of screening for prostate cancer using the digital rectal examination. J. Urol. 141, 1136–1138 (1989).

    Article  CAS  Google Scholar 

  17. Gosselaar, C., Kranse, R., Roobol, M. J., Roemeling, S. & Schröder, F. H. The interobserver variability of digital rectal examination in a large randomized trial for the screening of prostate cancer. Prostate 68, 985–993 (2008).

    Article  CAS  Google Scholar 

  18. Vickers, A. J. et al. Impact of recent screening on predicting the outcome of prostate cancer biopsy in men with elevated PSA: data from the European Randomized Study of Prostate Cancer Screening in Gothenburg, Sweden. Cancer 116, 2612–2620 (2010).

    PubMed  PubMed Central  Google Scholar 

  19. You, J. et al. Innovative biomarkers for prostate cancer early diagnosis and progression. Crit. Rev. Oncol. Hematol. 73, 10–22 (2010).

    Article  Google Scholar 

  20. Edge, S. B. et al. (eds) AJCC Cancer Staging Manual (Springer, New York, 2010).

    Google Scholar 

  21. Gleason, D. F. & Mellinger, G. T. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J. Urol. 111, 58–64 (1974).

    Article  CAS  Google Scholar 

  22. Schmidt, C. Gleason scoring system faces change and debate. J. Natl Cancer Inst. 101, 622–629 (2009).

    Article  Google Scholar 

  23. Cheng, L., Montironi, R., Bostwick, D. G., Lopez-Beltran, A. & Berney, D. M. Staging of prostate cancer. Histopathology 60, 87–117 (2012).

    Article  Google Scholar 

  24. Bostwick, D. G. et al. Prognostic factors in prostate cancer. College of American Pathologists Consensus Statement 1999. Arch. Pathol. Lab. Med. 124, 995–1000 (2000).

    CAS  PubMed  Google Scholar 

  25. Shen, M. M. & Abate-Shen, C. Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24, 1967–2000 (2010).

    Article  CAS  Google Scholar 

  26. Porkka, K. P. & Visakorpi, T. Molecular mechanisms of prostate cancer. Eur. Urol. 45, 683–691 (2004).

    Article  CAS  Google Scholar 

  27. Reynolds, M. A. Molecular alterations in prostate cancer. Cancer Lett. 271, 13–24 (2008).

    Article  CAS  Google Scholar 

  28. Ho, C. M. & Weilbaecher, A. Patents versus patients: must we choose? Ann. Health Law 18, i–xv (2009).

    PubMed  Google Scholar 

  29. Mejer, M. & van Pottelsberghe de la Potterie, B. Patent backlogs at USPTO and EPO: systemic failure vs deliberate delays. World Patent Inf. 33, 122–127 (2011).

    Article  Google Scholar 

  30. Sternitzke, C. Reducing uncertainty in the patent application procedure—insights from invalidating prior art in European patent applications. World Patent Inf. 31, 48–53 (2009).

    Article  CAS  Google Scholar 

  31. Madu, C. O. & Lu, Y. Novel diagnostic biomarkers for prostate cancer. J. Cancer 1, 150–177 (2010).

    Article  Google Scholar 

  32. Busse, U., Chypre, C. & Fradet, Y. PCA3 messenger RNA species in benign and malignant prostate tissues. US Patent 7,368,545 (2010).

  33. Daly, J. R., Jost, M., Reynolds, M. A., Groskopf, J. & Rittenhouse, H. PCA3: from basic molecular science to the clinical lab. Cancer Lett. 301, 1–6 (2011).

    Article  Google Scholar 

  34. PROGENSA®PCA3 featured at European Association of Urology congress in Paris. DiagnoCure [online], (2012).

  35. Pettersson, K., Lilja, H., Lövgren, T. & Niemelä, P. Antibody, immunoassay and method for prostate cancer detection. US Patent 7,872,104 (2001).

  36. Vickers, A. J. et al. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden. BMC Med. 6, 19–29 (2008).

    Article  Google Scholar 

  37. Hessels, D., Verhaegh, G., Schalken, J. A. & Witjes, A. J. mRNA ratios in urinary sediments and/or urine as a prognostic and/or theranostic marker for prostate cancer. US Patent 7,960,109 (2005).

  38. Zhang, Z., Barnhill, S. D., Madyastha, R. & Zhang, H. Methods for diagnosing cancer by measuring creatine kinase. US Patent 6,309,816 (1998).

  39. Tewari, P. Detection of PSA-.α.2-macroglobulin complex in a biological fluid. US Patent 6,548,260 (1998).

  40. Griffiths, K. & Turkes, A. T. Detection of prostate cancer measuring PSA/IGF-1 ratio. European Patent 1,218,749 (2000).

  41. Duan, X., Kim, N. & Wolfert, R. L. Cln101 antibody compositions and methods of use alone and in combination with prostate specific antigen and other cancer markers. US Patent 7,560,531 (2004).

  42. Stearns, M., Hu, Y. & Wang, M. Prostate cancer-related compositions, methods and kits based on DNA macroarray proteomics platforms. US Patent 7,939,274 (2010).

  43. Saatcioglu, F. Prostate-specific or testis-specific nucleic acid molecules, polypeptides, and diagnostic and therapeutic methods. US Patent 7,611,892 (2006).

  44. Sidransky, D. Method of detection of prostate cancer. US Patent 7,524,633 (2007).

  45. Jerónimo, C. et al. Quantitation of GSTP1 methylation in non-neoplastic prostatic tissue and organ-confined prostate adenocarcinoma. J. Natl Cancer Inst. 93, 1747–1752 (2001).

    Article  Google Scholar 

  46. Tsujikawa, K., Yamamoto, H. & Konishi, N. Method for diagnosis of prostate cancer. European Patent 1,862,804 (2006).

  47. Castellani, L. W. et al. Apolipoprotein AII is a regulator of very low density lipoprotein metabolism and insulin resistance. J. Biol. Chem. 283, 11633–11644 (2008).

    Article  CAS  Google Scholar 

  48. Semmes, J. O., Malik, G. & Ward, M. D. Apolipoprotein A-II isoform as a biomarker for prostate cancer. European Patent 1,838,867 (2006).

  49. An, G. & Veltri, R. Prostate-specific gene for diagnosis, prognosis and management of prostate cancer. US Patent 7,993,830 (2007).

  50. Thompson, T. C. Methods and compositions for diagnosis and monitoring of prostate cancer progression by detection of serum caveolin. US Patent 7,462,491 (2004).

  51. Golub, T. R., Febbo, P. G., Ross, K. N. & Sellers, W. R. Prostate cancer diagnosis and outcome prediction by expression analysis. US Patent 7,501,248 (2005).

  52. Penny, K. L. et al. mRNA expression signature of gleason grade predicts lethal prostate cancer. J. Clin. Oncol. 29, 2391–2396 (2011).

    Article  Google Scholar 

  53. Tempst, P. & Villanueva, J. Methods of detection of cancer using peptide profiles. US Patent 7,972,770 (2006).

  54. Mikolajczyk, S. D., Wang, T. J., Rittenhouse, H. G., Wolfert, R. L. & Slawin, K. Forms of prostate specific antigen (PSA) specific for benign prostatic hyperplasia (BPH) and methods of using such. US Patent 6,482,599 (1999).

  55. Amano, J., Hirano, K. & Sugimoto, I. Method of distinguishing prostate cancer from benign prostatic hypertrophy. US Patent 8,030,085 (2008).

  56. Chudin, E., Lozach, J., Fan, J. & Bibikova, M. Gene expression profiles to predict relapse of prostate cancer. US Patent 7,914,988 (2007).

  57. Keller, E. T. & Fu, Z. Systems and methods for detecting and regulating metastasis. US Patent 7,407,763 (2005).

  58. Bao, L. & Wang, D. G. Pin 1 as a marker for prostate cancer. US Patent 7,592,145 (2006).

  59. Siegler, K. M. Serum macrophage migration inhibitory factor (MIF) as marker for prostate cancer. US Patent 7,361,474 (2003).

  60. Reed, J. C. & Krajewske, S. Methods for determining the prognosis for patients with a prostate neoplastic condition using inhibitor of apoptosis polypeptides. US Patent 7,704,700 (2003).

  61. O'Riordan, M. X. D., Bauler, L. D., Scott, F. L. & Duckett, C. S. Inhibitor of apoptosis (IAP) proteins in eukaryotic evolution and development: a model of thematic conservation. Dev. Cell 15, 497–508 (2008).

    Article  CAS  Google Scholar 

  62. Rubin, M. A. & DeMichelis, F. Biomarkers for predicting prostate cancer progression. US Patent 7,803,552 (2009).

  63. Glinsky, G. V., Glinskii, A. B., Stephenson, A. J., Hoffman, R. M. & Gerald, W. L. Gene expression profiling predicts clinical outcome of prostate cancer. J. Clin. Invest. 113, 913–923 (2004).

    Article  CAS  Google Scholar 

  64. Li, C. & Wong, W. H. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc. Natl Acad. Sci. USA 98, 31–36 (2001).

    Article  CAS  Google Scholar 

  65. Wang, D., Herzenberg, L. A., Peehl, D. M. & Herzenberg, L. A. Prostate cancer glycan markers and autoantibody signatures. US Patent 7,981,625 (2009).

  66. Neagu, M., Constantin, C., Tanase, C. & Boda, D. Patented biomarker panels in early detection of cancer. Recent Pat. Biomark. 1, 10–24 (2011).

    CAS  Google Scholar 

  67. US Department of Heath and Human Services, FDA, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research & Center for Devices and Radiological Health. Guidance for industry: pharmacogenomic data dubmissions [online], (2005).

  68. European Medicines Agency. Guideline on the validation of bioanalytical methods [online], (2011).

  69. US Department of Heath and Human Services, FDA, Center for Drug Evaluation and Research & Center for Veterinary Medicine. Guidance for industry: bioanalytical method validation [online], (2001).

  70. Valentin, M. A., Ma, S., Zhao, A., Legay, F. O. & Avrameas, A. Validation of immunoassay for protein biomarkers: bioanalytical study plan implementation to support pre-clinical and clinical studies. J. Pharm. Biomed. Anal. 55, 869–877 (2011).

    Article  CAS  Google Scholar 

  71. Swanson, G. P., Yu, C., Kattan, M. W. & Hermans, M. R. Validation of postoperative nomograms in prostate cancer patients with long-term follow-up. Urology 78, 105–109 (2011).

    Article  Google Scholar 

  72. Specht, M. C., Kattan, M. W., Gonen, M., Fey, J. & Van Zee, K. J. Predicting nonsentinel node status after positive sentinel lymph biopsy for breast cancer: clinicians versus nomogram. Ann. Surg. Oncol. 12, 654–659 (2005).

    Article  Google Scholar 

  73. Vickers, A. J. Prediction models in cancer care. CA Cancer J. Clin. 61, 315–326, (2011).

    PubMed  PubMed Central  Google Scholar 

  74. Garofolo, F., Smeraglia, J., Briggs, R., Seymour, M. & Hill, H. Conference report: discussion on harmonization and globalization of bioanalytical guidances at the 19th International Reid Bioanalytical Forum. Bioanalysis 3, 2717–2720 (2011).

    Article  CAS  Google Scholar 

  75. US Department of Heath and Human Services, FDA, Center for Drug Evaluation and Research & Center for Biologics Evaluation and Research. Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics [online], (2007).

  76. Chowdhury, F., Williams, A. & Johnson, P. Validation and comparison of two multiplex technologies, Luminex and Mesoscale Discovery, for human cytokine profiling. J. Immunol. Methods 340, 55–64 (2009).

    Article  CAS  Google Scholar 

  77. Kruse, N., Schulz-Schaeffer, W. J., Schlossmacher, M. G. & Mollenhauer, B. Development of electrochemiluminescence-based singleplex and multiplex assays for the quantification of α-synuclein and other proteins in cerebrospinal fluid. Methods http://dx.doi.org/10.1016/j.ymeth.2012.03.016

  78. Semenuk, M. A. et al. Translating cancer biomarker discoveries to clinical tests: what should be considered? Recent Pat. Biomark. 1, 222–240 (2011).

    Article  CAS  Google Scholar 

  79. Schröder, F. H. et al. Screening and prostate-cancer mortality in a randomized European study. N. Engl. J. Med. 26, 1320–1328 (2009).

    Article  Google Scholar 

  80. Stephenson, A. J. et al. Defining biochemical recurrence of prostate cancer after radical prostatectomy: a proposal for a standardized definition. J. Clin. Oncol. 24, 3973–3978 (2006).

    Article  CAS  Google Scholar 

  81. Lilja, H., Ulmert, D. & Vickers, A. J. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat. Rev. Cancer 8, 268–278 (2008).

    Article  CAS  Google Scholar 

  82. Horwitz, E. M. et al. Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis. J. Urol. 173, 797–802 (2005).

    Article  Google Scholar 

Download references

Acknowledgements

The authors are supported by the Health Research Board (HRB) as part of the HRB–Science Foundation Ireland translational research award (TRA/2010/18).

Author information

Authors and Affiliations

  1. University College Dublin School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, 4, Ireland

    Lisa Murphy & R. William Watson

Authors
  1. Lisa Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. William Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L. Murphy researched the data for this article. Both authors wrote and edited the manuscript before submission as well as contributing to the discussion of its content.

Corresponding author

Correspondence to Lisa Murphy.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murphy, L., Watson, R. Patented prostate cancer biomarkers. Nat Rev Urol 9, 464–472 (2012). https://doi.org/10.1038/nrurol.2012.130

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrurol.2012.130

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing