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A Simple, Rapid Diagnostic Test for the Accurate & Early Detection of Prostate Cancer

IP.com Disclosure Number: IPCOM000241500D
Publication Date: 2015-May-07

Publishing Venue

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Abstract

Prostate cancer (PC) is the second most common cause of cancer related deaths in men. The current standard diagnostic test, involves a digital rectal examination (DRE) in combination with the detection of a key biomarker prostate specific antigen (PSA). Unfortunately, the PSA test is associated with a number of key limitations and these limitations have justified the discovery and evaluation of new potential biomarkers for PC. However, despite the recent publication of several alternative putative biomarkers of there remains an almost total clinical dependence on DRE together with PSA measurement. Thus, we have identified the possible diagnostic potential of Engrailed-2 (EN-2) protein, a homeodomain-containing transcription factor secreted into the urine by men with prostate cancer using a new diagnostic approach. This invention describes a novel diagnostic test for EN-2 specifically secreted by cancerous prostate cells that incorporates the application and storage of urine on cellulose-based dry, solid supports such as nitrocellulose. Detection of EN-2 would involve a simple urine-based, point of care, lateral flow device together with associated antibodies, aptamers or other molecules designed to bind specifically to EN-2. Detection will be achieved using appropriate reporter groups and enzymes that facilitate the generation of an optical or visual signal. The sensitivity, speed and specificity of an EN-2-based urine test involving lateral flow would make this diagnostic tool attractive as a simple screening tool in the community at point of care. The associated ease of use and sensitivity of this test will reduce the need for DRE as the primary screening method. Additionally, this test would reduce the need for specialised laboratory and healthcare professionals required to perform tests, analyse data and interpret results, thereby increasing patient access to PC diagnosis and treatment in less resource rich areas of the world. The storage of urine on the solid support material would also facilitate the detection of EN-2 mRNA expression using technologies such as reverse transcription PCR and NASBA isothermal amplification. These methods can be performed using a direct amplification protocol in which a portion of the dry solid support containing urine is added directly to the amplification reaction in which the associated reagents and enzymes etc are provided in a dry lyophilised format. The simple addition of water and the solid support generates a fully configured diagnostic test. This invention therefore describes new point of care lateral flow and molecular diagnostic tests for the early diagnosis of prostate cancer using the biomarker Engrailed-2. Furthermore, we describe a potential risk index that is of significant value for predictive early care and patient treatment and management.

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A Simple, Rapid Diagnostic Test for the Accurate & Early Detection of Prostate Cancer

Introduction

Prostate cancer (PC) is the second most common cause of cancer related deaths in men, with approximately 1,000,000 new cases diagnosed globally during 2008. Localized, organ-confined PC can be cured in a significant proportion of patients, provided that PC is detected at an early stage. However, advanced and metastatic PC continues to be associated with extremely poor prognosis.

Serum prostate-specific antigen PSA is currently used as a cancer marker for the initial diagnosis of PC, as a means to monitor patient response to treatment and as a test to predict PC risk and treatment outcome. Nonetheless, PSA as a diagnostic marker for PC has many disadvantages; it is prostate specific and not a prostate cancer specific biomarker and is frequently raised in non-cancer conditions such as benign hypertrophy and prostatitis. Therefore detection of PSA lacks both sensitivity and specificity to accurately detect the presence of PC, with diagnostic assays requiring adjustments for both age and prostate volume. In recent years these limitations have stimulated must debate about the efficacy of PSA as an effective screening tool for PC.

A widely accepted serum PSA cut-off of 4 ng/ml has some predictive value for the detection of PC but, only 15% of prostate cancers were detected at biopsy based on PSA detection during a UK-Wide National Prostate Cancer Prevention Trial.

Therefore there is a need for new markers and diagnostic tests to overcome at least some of the limitations of serum PSA. Such markers could include Engrailed-2 (EN-2). A significant advantage of EN-2 is that it is present in the urine of men suffering from PC and therefore represents a potentially less invasive initial diagnostic test compared to serum PSA.

In addition to EN-2, other potential PC-specific biomarkers have been identified, these include; PCA3, human kallikrein- related peptidase 2 and urokinase-type activator receptor. These biomarkers may be useful to identify particularly aggressive forms of PC and can also be considered as potential candidates for this invention.

Summary of the invention

Prostate cancer (PC) is the second most common cause of cancer related deaths in men. The current standard diagnostic test, involves a digital rectal examination (DRE) in combination with the detection of a key biomarker prostate specific antigen (PSA). Unfortunately, the PSA test is associated with a number of key limitations and these limitations have justified the discovery and evaluation of new potential biomarkers for PC. However, despite the recent publication of several alternative putative biomarkers of there remains an almost total clinical dependence on DRE together with PSA measurement. Thus, we have identified the possible diagnostic potential of Engrailed-2 (EN-2) protein, a homeodomain-containing transcription factor secreted into the urine by men with prostate cancer using a...