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

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

Article highlights.

• MMPs are classified in the family of zinc-dependent endopeptidases, which can degrade various components of an ECM and a basement membrane.

• MMPs are highly expressed in malignant tumors and are related to cancer patients’ malignant phenotype and poor prognosis.

• Blocking the expression or activity of MMPs may be a promising strategy for cancer treatment.

• MMPIs can be divided into four types: peptidomimetics, nonpeptidomimetics, tetracycline-like derivatives, and BPs.

• The failed application of MMPIs to cancer treatment may result from their lack of selectivity for MMPs. Therefore, developing MMPIs that have selectivity is a new direction for cancer treatment.

This box summarizes key points contained in the article.

Declaration of Interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.