Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

TY - JOUR

T1 - Cancer therapy trials employing level-of-evidence-1 disease forecast cancer biomarkers uPA and its inhibitor PAI-1

AU - Schmitt, Manfred

AU - Harbeck, Nadia

AU - Brünner, Nils

AU - Jänicke, Fritz

AU - Meisner, Christoph

AU - Mühlenweg, Bernd

AU - Jansen, Heike

AU - Dorn, Julia

AU - Nitz, Ulrike

AU - Kantelhardt, Eva J

AU - Thomssen, Christoph

PY - 2011/7

Y1 - 2011/7

N2 - Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) are two of the few tumor tissue-associated cancer biomarkers that have been evaluated successfully and extensively in many preclinical and clinical studies for their clinical utility. Most of the studies have been conducted in early breast cancer to demonstrate the prognostic and predictive value for this malignancy. As a result of these investigations, uPA and PAI-1 have reached the highest level of clinical evidence, level of evidence 1. This article sheds light on the current status of major clinical Phase II and III breast cancer therapy trials (Chemo-N0, NNBC-3 and Plan B), and introduces ongoing clinical trials targeting uPA in advanced cancers of the breast and pancreas, employing synthetic small-size drugs to counteract uPA activity (WX-UK1, Mesupron(®)). The therapeutic effect of a uPA-derived small-size synthetic peptide (Å6) is tested in advanced ovarian cancer patients.

AB - Clinical research on cancer biomarkers is essential in understanding recent discoveries in cancer biology and heterogeneity of the cancer disease. However, there are only a few examples of clinically useful studies that have identified cancer biomarkers with clinical benefit. Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) are two of the few tumor tissue-associated cancer biomarkers that have been evaluated successfully and extensively in many preclinical and clinical studies for their clinical utility. Most of the studies have been conducted in early breast cancer to demonstrate the prognostic and predictive value for this malignancy. As a result of these investigations, uPA and PAI-1 have reached the highest level of clinical evidence, level of evidence 1. This article sheds light on the current status of major clinical Phase II and III breast cancer therapy trials (Chemo-N0, NNBC-3 and Plan B), and introduces ongoing clinical trials targeting uPA in advanced cancers of the breast and pancreas, employing synthetic small-size drugs to counteract uPA activity (WX-UK1, Mesupron(®)). The therapeutic effect of a uPA-derived small-size synthetic peptide (Å6) is tested in advanced ovarian cancer patients.

KW - Animals

KW - Antineoplastic Agents

KW - Clinical Trials as Topic

KW - Humans

KW - Neoplasms

KW - Plasminogen Activator Inhibitor 1

KW - Protein Structure, Secondary

KW - Protein Structure, Tertiary

KW - Tumor Markers, Biological

KW - Urokinase-Type Plasminogen Activator

U2 - 10.1586/erm.11.47

DO - 10.1586/erm.11.47

M3 - Journal article

C2 - 21745015

SN - 1473-7159

VL - 11

SP - 617

EP - 634

JO - Expert Review of Molecular Diagnostics

JF - Expert Review of Molecular Diagnostics

IS - 6

ER -