Method for biomarker and drug-target discovery for prostate cancer diagnosis and treatment as well as biomarker assays determined therewith

Abstract

The invention relates to a method for the determination of a cancer diagnostic / therapeutic biomarker assay and drug-targets including the following steps: (a) identification of potential candidate protein / peptide biomarkers and drug-targets based on the measurement of protein / peptide constituent concentrations in tissue sample proteomes as well as serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy non-human mammalian individuals as well as from cancerous non-human mammalian individuals and qualitatively selecting as potential candidate protein / peptide biomarkers those which show a pronounced differential behaviour between healthy and cancerous sample proteomes; (b) optional verification of the potential candidate protein / peptide biomarkers as identified in step (a) by quantitative mass spectrometric measurement of the potential candidate protein biomarkers in serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy non-human mammalian individuals as well as from cancerous non-human mammalian individuals and selecting as candidate protein / peptide biomarkers those which show a mass-spectrometrically measurable quantitative differential behaviour between healthy and cancerous sample proteomes; (c) validation of the candidate protein / peptide biomarkers as identified in step (a), or as optionally verified in step (b), by mass spectrometric measurement and / or antibody-based assays such as an Enzyme-Linked Immunosorbent Assay (ELISA) determination of the candidate protein biomarkers in serum, plasma or any other derivatives of blood, or blood itself sample proteomes derived from healthy human individuals as well as from cancerous human individuals and selecting as protein / peptide biomarkers those which show a mass-spectrometrically measurable and / or antibody-based assay detectable differential behaviour between healthy and cancerous sample proteomes; (d) application of statistical methods to uncover single or groups of protein / peptide biomarkers as validated in step (c) as signatures for the detection of patients with cancer. The invention furthermore relates to specific biomarker assays for the highly reliable diagnosis of cancer, specifically of localized or non-localized prostate cancer, using human serum, plasma or any other derivatives of blood, or blood itself.

Description

TECHNICAL FIELD[0001]The present invention relates to the field of methods for the determination of biomarker assays and / or drug-targets for the diagnosis of cancer and its treatment and / or prognosis, specifically of prostate cancer, be it localized or non-localized prostate cancer. A further object of the present invention is to propose specific biomarker assays for these diagnostic purposes and / or patient stratification as well as methods for diagnosis using these specific biomarker assays.BACKGROUND OF THE INVENTION[0002]The diagnosis and treatment of prostate cancer, despite decennial research efforts, are still a major challenge in the clinics. Prostate cancer progression is unfortunately silent, and an early detection of faster progressing and potentially dangerous lesions is crucial for the patient's health, since complete remission and cure from the disease is possible only at early stages of the disease.[0003]The best noninvasive diagnostic test available for prostate cance...

AI Technical Summary

Benefits of technology

[0016]One of the gists of the present invention is therefore the concept to increase the accuracy of the non-invasive diagnostic procedure for the detection of (prostate) cancer on the one hand, and to identify new therapeutical / imaging targets used in the clinical practice. We have established a protocol for (prostate) cancer biomarkers and / or drug-targets identification, which is summarized in FIG. 1, which will be discussed in more detail further below. This approach is based on three major aspects:(I) a translational approach based on the initial identification of candidate biomarkers and / or drug-targets, in vivo using a defined genetic mouse model and subsequent validation in human clinical samples;(II) cutting edge mass spectrometry-based methodologies and bioinformatics methods established in our lab for the isolation, identification and quantitation of N-linked glycoproteins followed by(III) multivariate statistical methods to uncover particular signatures for the detection of patients with prostate cancer.

[0035]To increase the reliability of such cancer diagnostic biomarker assay, it can be combined with an affinity reagent-based assay, e.g. an antibody-based assay such as Enzyme-Linked Immunosorbent Assay (ELISA) for the detection of further systems such as Prostate Specific Antigen (PSA). Also multiplexing techniques of a series of antibodies for example using bead techniques are possible in this respect.

Problems solved by technology

From a practical point of view the only limitation can sometimes be that a model system should be available which can be used for the translational approach as described below.

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