Clinical Research Unit, Department of Obstetrics and Gynecology (Frauenklinik), Klinikum rechts der Isar of the Technical University of Munich, Ismaninger Strasse 22, D-81675 Munich, Germany.
Expert Rev Mol Diagn. 2011 Jul;11(6):617-34. doi: 10.1586/erm.11.47.
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.
癌症生物标志物的临床研究对于理解癌症生物学的最新发现和癌症疾病的异质性至关重要。然而，仅有少数具有临床获益的癌症生物标志物的临床研究被证明是有用的。尿激酶型纤溶酶原激活物（uPA）及其抑制剂纤溶酶原激活物抑制剂 1（PAI-1）是两种为数不多的已在许多临床前和临床研究中成功且广泛评估其临床实用性的肿瘤组织相关癌症生物标志物。这些研究大多在早期乳腺癌中进行，以证明其对这种恶性肿瘤的预后和预测价值。由于这些研究，uPA 和 PAI-1 达到了最高水平的临床证据，证据水平 1。本文阐述了当前主要的 II 期和 III 期乳腺癌治疗临床试验（Chemo-N0、NNBC-3 和 Plan B）的现状，并介绍了针对乳腺癌和胰腺进展期癌症的正在进行的 uPA 靶向临床试验，使用合成的小分子药物来拮抗 uPA 活性（WX-UK1、Mesupron(®)）。uPA 衍生的小分子合成肽（Å6）在晚期卵巢癌患者中的治疗效果正在进行测试。
