antiangiogenesis

Antiangiogenesis refers to strategies that inhibit angiogenesis, the growth of new blood vessels from pre-existing vasculature. These approaches aim to deprive pathological tissues of blood supply, slowing growth in cancer and other diseases characterized by abnormal vessel formation, while attempting to preserve normal vascular development.

Therapeutic strategies include blocking vascular endothelial growth factor (VEGF) signaling with monoclonal antibodies (for example, bevacizumab), soluble decoy receptors (aflibercept), and receptor tyrosine kinase inhibitors that target VEGF receptors (such as sunitinib, sorafenib, and pazopanib). Other approaches involve anti-angiogenic agents like thalidomide and its derivatives, as well as agents that interfere with endothelial cells, pericyte interaction, or extracellular matrix remodeling. In ophthalmology, intravitreal VEGF inhibitors are used to treat age-related macular degeneration and diabetic retinopathy; in oncology, anti-VEGF therapy is employed across various cancers, often in combination with chemotherapy or immunotherapy.

Mechanisms include reduction of endothelial proliferation and vascular permeability, disruption of abnormal tumor vasculature, and in some cases vascular normalization that can improve drug delivery. Limitations include the development of resistance through alternative pro-angiogenic pathways, vessel co-option, or vascular mimicry, and adverse effects such as hypertension, thromboembolism, wound healing impairment, hemorrhage, proteinuria, and thrombotic microangiopathy.

History and status: the concept was proposed by Judah Folkman in 1971; clinical approvals for VEGF-targeted agents began in the early 2000s. Research continues on optimal dosing (for example metronomic schedules), combination regimens, predictive biomarkers, and managing toxicity.