Biomarkers in Prostate Cancer

by Sheng-Fei Oon, Conway Institute of Biomolecular and Biomedical Research, University College Dublin

Sheng-Fei Oon used TUF funding to help research new and more accurate ways of testing for prostate cancer - with promising early results.

Prostate cancer is the most common solid-organ malignancy among men in developed countries. The current annual incidence in Ireland is 2,450, and the National Cancer Registry predicts that the number of prostate cancer cases will increase by 275% to 18,436 by 2020.

This increase is of major concern as the detection and treatment of prostate cancer poses many dilemmas and controversy exists over the effectiveness of screening regimens using the current biomarker, prostate-specific antigen (PSA), which, as its name suggests, is specific to the prostate gland, but not to prostate cancer. PSA is raised in other common benign conditions of the prostate including benign prostatic hyperplasia and prostatitis, and up to one third of men with prostate cancer have a normal PSA.

Several large-scale trials have shown that common diagnostic standards for prostate cancer all have low sensitivities.

Luckily, not all prostate cancers require invasive therapy, as the majority of patients have low-grade, indolent cancers that persist throughout life without causing any signs or symptoms. However, a small proportion of men will present with a higher-grade, aggressive prostate cancer that requires urgent curative therapy, as this cancer is more likely to cause symptoms, spread to other organs, and result in death or disability without treatment.

Unfortunately, it is difficult to determine indolent from significant disease. Current paradigms use a combination of PSA, clinical examination of the prostate and Gleason scoring of needle biopsy to help the clinician make a more accurate judgement of cancer significance, However, several large-scale trials have shown that these diagnostic standards all have low sensitivities.

The Gleason scale is a system in which each histological specimen is assigned a score from 2 to 10 according to the aggressiveness of the cancer. Using this system, prostate cancer cells with scores of 6 or less are considered indolent, whereas cells with scores of 7 or more are considered aggressive.

To overcome this problem, we have begun a biomarker discovery programme at the University College Dublin Conway Institute, and we have identified a panel of expressed proteins in serum that could distinguish between insignificant and aggressive cancers with a high accuracy (Gleason 5 versus Gleason 7 tumours, area under the curve 0.752).

If successful, we should be able to develop a serum-based assay that will help reduce the need for invasive needle biopsies...

However, all newly developed biomarker panels must also be tested on an external source of samples to ensure that the results obtained are similar. I have obtained serum from collaborators in Austria and Australia and am now validating the biomarker panel in these patients.

If this biomarker panel is successful, we should be able to develop a serum-based assay that will help to reduce the need for invasive needle biopsies for the determination of prostate cancer aggressiveness and that will improve the accuracy and sensitivity of diagnosis so that more aggressive cancers will be identified and fewer unnecessary biopsies and surgical interventions will be needed.

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