Connor Purcell, Dinara Ryspayeva, Jay Gopal, Andrea Schmidt, Philippa Vaughn-Beaucaire, Audrey Y. Su, Sean E. Lawler, William J. MacDonald, Maximillian Pinho-Schwerrman, Wafik S. El‐Deiry, Attila A. Seyhan
The tumor vasculature is a dynamic and heterogeneous component of the tumor microenvironment (TME) that influences tumor progression, immune infiltration, metastasis, and therapeutic response. This review explores the factors that contribute to the unique vascular characteristics of the TME and highlights the potential for molecular and imaging biomarkers to predict treatment outcomes. We discuss structural and functional abnormalities of tumor vessels, including altered architecture, permeability, interstitial pressure, endothelial phenotype, and impaired drug delivery. We also examine angiogenic signaling through hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), in addition to emphasizing non-angiogenic mechanisms such as vessel co-option. The review then turns to the current clinical landscape of angiogenesis, assessing the success and limitations of current therapies, emerging treatment strategies, biomarkers associated with angiogenesis, and AI-assisted prognostication. The establishment and clinical utilization of angiogenesis and tumor vasculature biomarkers is critical for disease diagnosis, prognosis, and the development of targeted therapies. This review ultimately aims to inform future innovation in vasculature-targeted therapies and their personalized clinical implementation to improve cancer care.