Matrix metalloproteinase inhibitors: a novel class of anticancer agents

Adv Enzyme Regul. 1995;35:293-301. doi: 10.1016/0065-2571(94)00022-u.

Abstract

Matrix metalloproteinase inhibitors represent a new therapeutic approach to the treatment of advanced cancer. These inhibitors block the activity of proteolytic enzymes, matrix metalloproteinases, used by tumor cells to break down and remodel tissue matrices during the process of metastatic spread. As such they were regarded initially as inhibitors of metastasis. However, recent studies have shown that these inhibitors can also act to inhibit tumor growth by (i) preventing local invasion and promoting stromal encapsulation and (ii) by inhibiting tumor neovascularization. Matrix metalloproteinase inhibitors therefore have the potential to halt tumor progression and it is possible to envision their use as a low toxicity complement to cytotoxic therapies. Batimastat (BB-94) is the first inhibitor of this class to enter clinical trial in cancer patients. In a phase I/II trial in patients with malignant ascites batimastat was well tolerated and there were preliminary signs of efficacy.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / pathology
  • Female
  • Humans
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / pathology
  • Metalloendopeptidases / antagonists & inhibitors*
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Metastasis
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Phenylalanine / analogs & derivatives*
  • Phenylalanine / pharmacology
  • Phenylalanine / therapeutic use
  • Protease Inhibitors / pharmacology*
  • Protease Inhibitors / therapeutic use
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use

Substances

  • Antineoplastic Agents
  • Protease Inhibitors
  • Thiophenes
  • Phenylalanine
  • batimastat
  • Metalloendopeptidases