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Matrix Metalloproteinases: A challenging paradigm of cancer management
Ali Alaseem1, Khalid Alhazzani2, Priya Dondapati3
1Rumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, Fort Lauderdale, FL 33314, USA; College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA; College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
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.
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