Tumor angiogenesis mediators

Tumor angiogenesis mediators are a diverse group of signaling molecules, primarily growth factors and cytokines, secreted by tumor cells and the surrounding stroma to stimulate the formation of new blood vessels [1]. This process, known as the angiogenic switch, is essential for tumor growth beyond a few millimeters, as it provides the necessary oxygen and nutrients while facilitating metabolic waste removal [2]. These mediators also play a critical role in systemic metastasis by providing routes for tumor cells to enter the circulatory system [1]. The most prominent mediator is Vascular Endothelial Growth Factor (VEGF), but others include Platelet-Derived Growth Factor (PDGF), Fibroblast Growth Factor (FGF), and Angiopoietins [3]. Therapeutic strategies targeting these mediators aim to starve the tumor by inhibiting the activation of their respective receptors [4]. This is typically achieved through monoclonal antibodies that sequester ligands or small molecule inhibitors that block intracellular kinase domains [4]. While effective in various malignancies, these therapies are often associated with class-specific toxicities such as hypertension and vascular complications [5]. These side effects occur because many of these mediators are also involved in maintaining normal physiological vasculature and blood pressure [5]. [1] Ferrara N. Endocr Rev. 2004; [2] Hanahan D, Weinberg RA. Cell. 2011; [3] Jayson GC, et al. Lancet. 2016; [4] Kerbel RS. N Engl J Med. 2008; [5] Chen HX, Cleck JN. Nat Rev Clin Oncol. 2009.

Other names

Angiogenic factorsPro-angiogenic factorsTumor vascularization factorsAngiogenic cytokines

Inhibition of pro-angiogenic signaling through ligand neutralization (e.g., monoclonal antibodies or decoy receptors) or inhibition of downstream receptor tyrosine kinase activity (e.g., small molecule inhibitors).