Matrix Metalloproteinases: A challenging paradigm of cancer management.

Abstract

Matrix metalloproteinases (MMPs) are members of zinc-dependent endopeptidases implicated in a variety of physiological and pathological processes. Over the decades, MMPs have been studied for their role in cancer progression, migration, and metastasis. As a result, accumulated evidence of MMPs incriminating role has made them an attractive therapeutic target. Early generations of broad-spectrum MMP inhibitors exhibited potent inhibitory activities, which subsequently led to clinical trials. Unexpectedly, these trials failed to meet the desired goals, mainly due to the lack of efficacy, poor oral bioavailability, and toxicity. In this review, we discuss the regulatory role of MMPs in cancer progression, current strategies in targeting MMPs for cancer treatment including prodrug design and tumor imaging, and therapeutic value of MMPs as biomarkers in breast, lung, and prostate cancers.

• Authors: Ali Alaseem, Khalid Alhazzani, Priya Dondapati, Saad Alobid, Anupam Bishayee, Appu Rathinavelu
• Journal: Seminars in cancer biology (Semin Cancer Biol) Vol. 56 Pg. 100-115 (06 2019) ISSN: 1096-3650 [Electronic] England
• PMID: 29155240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Biomarkers
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases

Topics

• Animals
• Biomarkers
• Disease Management
• Disease Progression
• Disease Susceptibility
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Matrix Metalloproteinase Inhibitors (pharmacology, therapeutic use)
• Matrix Metalloproteinases (chemistry, genetics, metabolism)
• Molecular Targeted Therapy
• Neoplasms (diagnosis, drug therapy, etiology, metabolism)
• Signal Transduction (drug effects)
• Structure-Activity Relationship