Combretastatin A4 is primarily investigated for its potent antitumor activity, especially in the field of cancer therapy. It functions by inhibiting tubulin polymerization, which disrupts the formation of the cellular cytoskeleton in rapidly dividing cells. This mechanism selectively targets tumor blood vessels, leading to vascular shutdown within the tumor. As a result, blood flow to the tumor is significantly reduced, causing necrosis of cancer cells. It has been developed as a prodrug (CA4P) for improved solubility and is used in clinical trials for various solid tumors, including ovarian, thyroid, and liver cancers. Its role as a vascular disrupting agent (VDA) makes it a promising candidate for combination therapies with chemotherapy, radiation, or immunotherapy, where it enhances treatment efficacy by attacking the tumor’s blood supply. Research also explores its potential in anti-angiogenic therapy, preventing the formation of new blood vessels that support tumor growth.