Matrix Metalloproteinases: A challenging paradigm of cancer management

Semin Cancer Biol. 2019 Jun:56:100-115. doi: 10.1016/j.semcancer.2017.11.008. Epub 2017 Nov 16.

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.

Keywords: Biomarker; Cancer; Matrix metalloproteinase; Matrix metalloproteinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

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

Substances

  • Biomarkers
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases