Matrix metalloproteinase inhibitors

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are associated with the tumorigenic process. MMPs degrade the extracellular matrix, promoting tumor invasion and metastasis. They also regulate host defense mechanisms and normal cell function; blocking all MMPs may not lead to a positive therapeutic outcome. Most clinical trials of MMP inhibitors (MMPIs) have yielded disappointing results, perhaps due to inappropriate study design or tumor staging, or to lack of selectivity. Positive results have been seen in gastric cancer with marimastat and in Kaposi's sarcoma with metastat. This review summarizes the current status of MMPIs.

Signal Transducer and Activator of Transcription 1 Activation in Endothelial Cells Is a Negative Regulator of Angiogenesis

“…Although IFN-g suppression of COX-2 induction by VEGF was not complete, it is possible that partial inhibition of COX-2 expression could impede prostaglandin synthesis. Likewise, partial suppression of MMP-2 expression by IFN-g could prevent migration and invasiveness of tumor cells (38).…”

Elastin Stabilization for Treatment of Abdominal Aortic Aneurysms

“…11 As a result of its multifactorial pathogenesis, antiin-flammatory agents, 12 proteinase inhibitors (such as tissue inhibitors of metalloproteinases [TIMPs]), and genetic and pharmacological inhibition of MMPs 13 have been tested as potential AAA treatments in experimental animals, but none has yet reached clinical application. Because long-term, adequate control of local inflammation and MMP activities may be difficult to achieve and may be accompanied by adverse side effects, 14 our hypothesis was that stabilization of aortic elastin in aneurysm-prone arterial segments offers potential for the development of safe and effective therapies for AAAs.…”

Therapeutic Targets: Progress of Their Exploration and Investigation of Their Characteristics

“…Blocking all MMPs may not lead to a positive therapeutic outcome. So far, most clinical trials of MMP inhibitors have not yielded good results, due primarily to the lack of subtype selectivity, bioavailability, and efficacy and in some cases inappropriate study design (Ramnath and Creaven, 2004). Intensive efforts are being directed at the discovery of potent, selective, orally bioavailable MMP inhibitors for the treatment of cancer.…”