Pharmacodynamic considerations in the use of matrix metalloproteinase inhibitors in cancer treatment

Expert Opin Drug Metab Toxicol. 2016;12(2):191-200. doi: 10.1517/17425255.2016.1131820. Epub 2016 Jan 11.

Abstract

Introduction: Matrix metalloproteinases (MMPs) are classified in the family of zinc-dependent endopeptidases, which can degrade various components of an extracellular matrix and a basement membrane. Studies have demonstrated that MMPs relate to the development of malignant tumors and induce angiogenesis, resulting in the invasion and metastasis of tumor cells. MMPs are highly expressed in malignant tumors and are related to cancer patients' malignant phenotype and poor prognosis. Therefore, blocking the expression or activity of MMPs may be a promising strategy for cancer treatment.

Areas covered: This study aimed to explain the MMP structure, regulatory mechanism, and carcinogenic effect; investigate the matrix metalloproteinase-inhibitors (MMPIs) that are currently used in clinical trials for cancer treatment; and summarize the trial results.

Expert opinion: Currently, the results of clinical trials that have used MMPIs as anticancer agents are unsatisfactory. However, MMPs remain an attractive target for cancer treatment. For example, development of the specific peptide or antibodies in targeting the hemopexin domain of MMP-2 may be a new therapeutic direction. The design and development of MMPIs that have selectivity will be the primary focus in future studies.

Keywords: Cancer; matrix metalloproteinases; matrix metalloproteinases inhibitor; pharmacodynamics.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Design
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinases / drug effects
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / enzymology
  • Neovascularization, Pathologic / pathology
  • Prognosis

Substances

  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • Matrix Metalloproteinases