Is there new hope for therapeutic matrix metalloproteinase inhibition?

By R. Vandenbroucke, C. Libert. Nature reviews. Drug discovery, 2014

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The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases (2020, background): “MMP inhibitors have often been administered too late to make a difference, as basic research was done in the early stages of the disease, and clinical research was intended to be a last aid in the treatment of terminal patients [79].”
Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives (2021, background): “Finally, regarding MMP therapies, the disappointing antitumor effects of current MMP inhibitors have been gradually reported, but several novel types are being translated into early clinical trials [364].”
Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers (2016, background): “The authors also listed suboptimal trial design, inadequate clinical endpoints, use of metabolically unstable MMP inhibitors, poor oral bioavailability, no effect, toxic adverse effects, and discrepancies between preclinical animal models and human patients.(319) In summary, while much effort has go”