Abstract
Introduction: The role of hrombospondin-1 (TSP1) as a major endogenous angiogenesis inhibitor has been confirmed by numerous studies and subsequent mechanistic discoveries. It has yielded a new class of potential drugs against cancer and other angiogenesis-driven diseases.Areas covered: An overview of TSP1 functions and molecular mechanisms, including regulation and signaling. Functions in endothelial and non-endothelial cells, with emphasis on the role of TSP1 in the regulation of angiogenesis and inflammation. The utility of duplicating these activities for drug discovery. Past and current literature on endogenous TSP1 and its role in the progression of cancer and non-cancerous pathological conditions is summarized, as well as the research undertaken to identify and optimize short bioactive peptides derived from the two TSP1 anti-angiogenic domains, which bind CD47 and CD36 cell surface receptors. Lastly, there is an overview of the efficacy of some of these peptides in pre-clinical and clinical models of angiogenesis-dependent disease.Expert opinion: It is concluded that TSP1-derived peptides and peptide mimetics hold great promise as future agents for the treatment of cancer and other diseases driven by excessive angiogenesis. They may fulfill unmet medical needs including neovascular ocular disease and the diseases of the female reproductive tract including ovarian cancer.
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