Tumor vasculature and local tissue DNA (None)

The target "Tumor vasculature and local tissue DNA" refers to a dual-mechanism therapeutic strategy that simultaneously disrupts the established blood vessel network of a tumor and causes direct damage to the genetic material of the surrounding malignant cells. This dual-targeting profile is the hallmark of second-generation vascular disrupting agents (VDAs), most notably OXi4503 (combretastatin A1 diphosphate). The vascular component of the target involves the drug binding to tubulin within the endothelial cells of the tumor's established blood supply, leading to rapid microtubule depolymerization, cell rounding, and the subsequent collapse of the vessel lumen, which induces extensive tumor ischemia and necrosis. Simultaneously, the agent or its metabolites (such as orthoquinones) act directly on the DNA of local tumor cells, causing strand breaks or oxidative damage. This combined mechanism is specifically designed to address the "viable rim" of tumor cells that often survives treatment with traditional VDAs by providing a direct cytotoxic hit to those remaining cells. Clinical development of drugs hitting this dual target has focused on solid tumors and hematological malignancies like acute myeloid leukemia (AML).

Other names

Tumor blood vessels and DNAVascular-disrupting and cytotoxic targetTubulin and DNA (dual target)

Dual mechanism involving: 1) Binding to the colchicine site of tubulin in endothelial cells to induce microtubule depolymerization and vascular collapse; 2) Metabolic activation to orthoquinone intermediates that cause direct DNA damage and oxidative stress in tumor cells.