Pigment epithelium-derived factor as a natural matrix metalloproteinase inhibitor: a comparison with classical matrix metalloproteinase inhibitors used for cancer treatment
Access Status
Authors
Date
2014Type
Metadata
Show full item recordCitation
Source Title
ISSN
School
Collection
Abstract
Objectives: In the 1990s, the discovery of the important role of matrix metalloproteinases (MMPs) in cancer angiogenesis, growth and metastasis galvanised research efforts to search for ways to inhibit these MMPs. To date, this has resulted in the investigation of approximately 50 MMPIs which have undergone various phases of clinical trials. However, despite a large body of research being devoted to discovery and development of MMPIs, results have largely not been supportive of this approach to anticancer treatment. Key findings: The reasons for the general failure of these drugs in clinical trials include various unwanted side-effects, the use of healthy volunteers to provide drug dosages which did not correctly reflect dosages for cancer patients, and the exclusion of patients with early stage cancer in clinical trials despite MMPs being determined to be critical for the angiogenic switch, a process associated with early tumour growth. In contrast, a naturally-occurring endogenous protein and a non-functional serine protease inhibitor (serpin), pigment epithelium-derived factor (PEDF), has been proposed for cancer therapy partly due to its ability to regulate specific MMPs central to cancer progression. Summary: PEDF has been found to specifically downregulate membrane-type I matrix metalloproteinase (MT1-MMP) and furthermore, potentially matrix metalloproteinase-2 (MMP-2), two of the most commonly implicated MMPs in neoplasia.
Related items
Showing items related by title, author, creator and subject.
-
Garratt, L.W.; Sutanto, E.N.; Ling, K.M.; Looi, K.; Iosifidis, T.; Martinovich, K.M.; Shaw, N.C.; Kicic-Starcevich, E.; Knight, D.A.; Ranganathan, S.; Stick, S.M.; Kicic, Anthony (2015)© ERS 2015. Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix ...
-
Banerjee, B.; Ling, K.; Sutanto, E.; Musk, M.; Yerkovich, S.; Hopkins, P.; Stick, S.; Kicic, Anthony; Chambers, D. (2011)Background: Long-term survival after lung transplantation is hindered by the development of bronchiolitis obliterans syndrome (BOS), and recent evidence suggests that dysregulated epithelial repair may underlie its ...
-
Sethi, G.; Shanmugam, M.; Ramachandran, L.; Kumar, Alan Prem; Tergaonkar, V. (2012)Increasing evidence from epidemiological, preclinical and clinical studies suggests that dysregulated inflammatory response plays a pivotal role in a multitude of chronic ailments including cancer. The molecular mechanism(s) ...