Suppression of inhibitors

US20010034327A1Inactive Publication Date: 2001-10-25BRUNNER NIELS +7
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Patent Information

Authority / Receiving Office
US · United States
Current Assignee / Owner
BRUNNER NIELS
Publication Date
2001-10-25
Estimated Expiration
Not applicable · inactive patent

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Abstract

The present invention relates to methods for inhibiting malignant tumour growth, invasion and / or metastasis in a patient, the method comprising suppressing the inhibitory activity of an inhibitor of a protease or of a non-proteolytic matrix-degrading enzyme (IPNME) in malignant tumour tissue or potential malignant tumour tissue. The suppression may be brought about by administering compounds interacting with the IPNME, but also administration of compounds interacting with transcription of genes encoding the IPNME is a possibility. The invention also relates to methods of selecting and identifying compounds in the therapeutical methods, as well of the use of such compounds in the treatment of malignancies.
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Description

[0001] In order to invade and spread, cancer cells must degrade extracellular matrix proteins. This degradation is catalyzed by the concerted action of several enzymes including proteases and non-proteolytic matrix-degrading enzymes e.g. metalloproteases such as interstitial collagenases, type IV collagenases and stromelysins, aspartic proteases such as cathepsin D, other degradative enzymes such as heperanase, and serine proteases such as plasmin (1, 73-76). Plasmin is formed from its precursor, plasminogen, by two activators, tissue-type plasminogen activator (tPA) which is involved in thrombolysis, and urokinase-type plasminogen activator (uPA) which plays a central role in tissue remodelling, including cancer invasion. The activation of plasminogen is regulated by two specific plasminogen activator inhibitors (PAI-1 and PAI-2). Both uPA and PAI-1 are present in various types of cancer tissue, and it was recently found that high levels of uPA and PAI-1 in breast cancer tissue eac...

Claims

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