Strategies to Target Matrix Metalloproteinases as Therapeutic Approach in Cancer

Methods Mol Biol. 2018:1731:325-348. doi: 10.1007/978-1-4939-7595-2_27.

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that are capable of degrading numerous extracellular matrix (ECM) components thus participating in physiological and pathological processes. Apart from the remodeling of ECM, they affect cell-cell and cell-matrix interactions and are implicated in the development and progression of various diseases such as cancer. Numerous studies have demonstrated that MMPs evoke epithelial to mesenchymal transition (EMT) of cancer cells and affect their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Various studies have suggested MMPs as suitable targets for treatment of malignancies, and several MMP inhibitors (MMPIs) have been developed. Although initial trials have failed to establish MMPIs as anticancer agents due to lack of specificity and side effects, new MMPIs have been developed with improved action that are currently being investigated. Furthermore, novel strategies that target MMPs for improving drug delivery and regulating their activity in tumors are presented. This review summarizes the implication of MMPs in cancer progression and discusses the advancements in their targeting.

Keywords: Cancer; Clinical trial; MMP; Therapeutic approach.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Clinical Trials as Topic
  • Disease Progression
  • Drug Delivery Systems / methods
  • Enzyme Activation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • MicroRNAs / metabolism
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Protein Domains / drug effects

Substances

  • Antineoplastic Agents
  • Matrix Metalloproteinase Inhibitors
  • MicroRNAs
  • Matrix Metalloproteinases