Matrix metalloproteinases as breast cancer drivers and therapeutic targets

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66 Scopus citations

Abstract

Members of the matrix metalloproteinase (MMP) family have been identified as poor prognosis markers for breast cancer patients and as drivers of many facets of the tumor phenotype in experimental models. Early enthusiasm for MMPs as therapeutic targets was tempered following disappointing clinical trials that utilized broad spectrum, small molecule catalytic site inhibitors. However, subsequent research has continued to define key roles for MMPs as breast cancer promoters, to elucidate the complex roles that that these proteins play in breast cancer development and progression, and to identify how these roles are linked to specific and unique biochemical features of individual members of the MMP family. Here, we provide an overview of the structural features of the MMPs, then discuss clinical studies identifying which MMP family members are linked with breast cancer development and new experimental studies that reveal how these specific MMPs may play unique roles in the breast cancer microenvironment. We conclude with a discussion of the most promising avenues for development of therapeutic agents capable of targeting the tumor-promoting properties of MMPs.

Original languageEnglish (US)
Pages (from-to)1144-1163
Number of pages20
JournalFrontiers in Bioscience - Landmark
Volume20
Issue number7
DOIs
StatePublished - Jun 1 2015

Keywords

  • Breast cancer
  • Cancer biomarkers
  • EMT
  • Epithelial mesenchymal transition
  • MMP inhibitors
  • MMPs
  • Matrix metalloproteinases
  • TIMPs
  • Tissue inhibitors of metalloproteinases
  • Tumor microenvironment
  • Tumor progression

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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