The environment where tumor cells thrive is highly dependent on the tumor's ability to co-opt existing blood vessels and promote development of new blood vessels. Thus a key to limiting the growth of existing tumors and stopping the spread of cancer involves targeting blood vessels within tumors. Previously this research identified a drug formulation that exerts some of its therapeutic effects through a mechanism that involves tumor specific vascular damage. This was a fortuitous and unexpected discovery and more research is needed to better understand this therapeutic effect. The formulation is composed of synthetic and naturally occurring biodegradable lipids (fat molecules) that self associate to form small (100 times smaller than a red blood cell) spheres which can enclose 10,000 or more drug molecules inside. This new formulation (called Irinophore C) will be tested in cancer patients for the first time next year (2010). Importantly, it is expected that other drug formulations can be designed to cause more selective damage to the blood vessels within tumors. Before this can be done, however, several important questions need to be answered: How does vascular damage occur? What are the biological consequences? What formulation parameters can be modified to achieve more selective damage? Answers to these questions will be used to help design drug candidates that achieve unmatched treatment outcomes when used to treat experimental models of aggressive cancers. This research is focused on developing drug candidates that have the potential to be effective in patients with relapsed and metastatic disease as well as patients with cancers that are not effectively treated with currently available drugs. The treatments developed will build on existing treatment standards which use multiple drugs to achieve significant increases in the time patients live free of detectable disease when treated at doses that have little or no impact on the patient's quality of life.