Endostatin in disease modulation: From cancer to beyond

Angiogenesis plays a pivotal role in various pathological conditions, making it a key target in therapeutic development. Anti-angiogenic therapies are gaining traction for their potential in treating a range of angiogenesis-dependent diseases. Among these, endogenous angiogenesis inhibitors, particularly endostatin, have garnered significant attention for their therapeutic potential. While extensively studied for its anti-angiogenic effects in cancer, endostatin also exhibits anti-atherosclerotic and anti-fibrotic properties, broadening its therapeutic scope. Despite the successful clinical use of recombinant human endostatin in China for nearly two decades, its broader therapeutic potential remains underexplored. Thus, this review delves into the multifaceted applications of endostatin, examining its role in ocular diseases, inflammation, reproductive disorders, and tumor angiogenesis. Furthermore, it provides a comprehensive overview of its emerging roles beyond angiogenesis, particularly in the context of atherosclerosis and fibroproliferative conditions. [Display omitted] •Endostatin shows promise in treating cancer, atherosclerosis, fibrosis, and various other angiogenesis-dependent diseases.•Endostar, a recombinant endostatin, has been used successfully in China for nearly 20 years in cancer therapy.•Despite initial global interest, the use of endostatin diminished with the development of new angiogenesis inhibitors.•The proven efficacy and safety of Endostatin variant in China suggest it should be reconsidered for wider international use.•Improved recombinant human endostatin (rhES) variants with better pharmacokinetics could expand its global adoption.