ASA404: A Promising Vascular-Disrupting Agent for Cancer Therapy

Scientists at the University of Auckland in New Zealand have developed a new compound, ASA404, which has shown great promise in targeting and treating cancer tumors. This compound, an analogue of flavone acetic acid, induces hemorrhagic necrosis of experimental tumors by simultaneously targeting vascular endothelial cells and macrophages within the tumor microenvironment. In a series of experiments, ASA404 demonstrated its ability to cause significant changes in tumor tissue, including decreases in tumor blood flow, increases in vascular permeability, and increases in vascular endothelial apoptosis. These effects were observed within 1 hour of administration, and over a slightly longer time scale, ASA404 also induced an increase in tumor concentrations of TNF and other cytokines. The researchers concluded that ASA404 has the potential to augment the antitumor effects of other agents in cancer treatment.

Key Takeaways:

• ASA404 is a novel compound developed as an analogue of flavone acetic acid, which targets at least two cell types - vascular endothelial cells and macrophages - within the tumor microenvironment.
• In murine tumors, ASA404 induces coordinated decreases in tumor blood flow, increases in vascular permeability, and increases in vascular endothelial apoptosis, all occurring within 1 hour of administration.
• ASA404 induces an increase in tumor concentrations of TNF and other cytokines over a slightly longer time scale.
• Phase I clinical trials confirmed its vascular effects in humans, and Phase II trials demonstrated its activity in combination with the cytotoxic agents carboplatin and paclitaxel.
• The molecular target of ASA404's action is not yet identified.
• The researchers concluded that studies of changes in tumor tissue following treatment with ASA404 either alone or combined with other agents will provide new insights into the dynamics of the tumor microenvironment.
• ASA404 has the potential to augment the antitumor effects of other agents in cancer treatment.

Statistics:

• Studies demonstrated that ASA404 induces a 1-hour decrease in tumor blood flow, increase in vascular permeability, and increase in vascular endothelial apoptosis.
• Over a slightly longer time scale, ASA404 induced an increase in tumor concentrations of TNF and a number of other cytokines.
• Phase I clinical trials confirmed ASA404's vascular effects in humans.
• Phase II trials demonstrated ASA404's activity in combination with carboplatin and paclitaxel.

Sources:

• Future Oncology, "ASA404: a tumor vascular-disrupting agent with broad potential for cancer therapy," 2010;6(10):1537-1543
• NewsRx.com, Gene Therapy Weekly, Copyright 2011, "ASA404: A Promising Vascular-Disrupting Agent for Cancer Therapy"