The process of formation of new blood vessels is called angiogenesis. Angiogenesis is essential for growth and multiplication of solid tumors. If size of the tumor is less than 2 mm3, growth factors and nutrients are supplied by diffusion. However, if the tumor size is larger, blood supply to the tumor needs to be established. Dependence of tumor cells on newly formed blood vessels for their growth and metastasis has resulted in focusing on ‘angiogenesis’ as a novel target for cancer treatment. Vascular disrupting agents is a new and promising class of targeted anticancer agents having antiangiogenic effect. These agents primarily act by disrupting the formed abnormal solid tumor vasculature by targeting the immature dysmorphic endothelial cells. They exert their anticancer effect by targeting new tumor blood vessels that are formed by angiogenesis, blocking the supply of blood to the formed tumor. This makes the tumor deprived of essential nutrients and oxygen, leading to tumor cell death. Vascular disrupting agents are primarily used in the treatment of different types of cancer such as ovarian cancer, thyroid cancer, liver cancer, colorectal cancer, glioblastoma, and renal cell carcinoma.
Vascular disrupting agents are of two types: small-molecule and ligand-directed vascular disrupting agents. Small-molecule vascular disrupting agents have been further classified into tubulin-binding agents and flavonoids. Tubulin binding agents act by selectively binding to the β-tubulin colchicine binding site, which weakens microtubules and leads to change in the 3-dimensional shape of endothelial cells. Endothelial cells interrupt the tumor blood vessel, thereby leading to necrosis of cancer cells within the tumor. Examples of tubulin-binding agents include combretastatin, crolibulin, verubulin, and fosbretabulin.
The other type of small-molecule vascular disrupting agents are flavonoids, which promote localized release of the tumor necrosis factor TNFα from nearby activated macrophage cells. Examples of flavonoids include 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) and icaritin/pexastimogene devacirepvec. Ligand-directed vascular disrupting agents primarily act by delivering toxic effects to tumor endothelium. The small-molecule vascular disrupting agents segment is expected to expand significantly during the forecast period, as a majority of molecules in the pipeline are small molecules. Additionally, high incidence and prevalence rate of cancer, increase in the demand for newer treatment options, and the large number of ongoing clinical trials boost the vascular disrupting agents market. However, unsatisfactory results of clinical trials and low availability of safety data restrain the vascular disrupting agents market.