One of the most fundamental issues concerning the clinical use of angiogenic inhibitors is uncovering the nature and dynamics of vessel regression in treated tumors. We undertake to determine whether angiogenic inhibitors regress only recently-developed vasculature, and therefore could not fully regress long-established tumors, or if particular inhibitors can also regress more mature tumor vasculature possessing pericytes and smooth muscle cells. We will also, using digitized imaging techniques, characterize induced structural alterations in tumor vasculature through quantification of vessel parameters e.g. area, diameter, segment length, etc. Insight into the mechanism of vessel regression will aid in optimizing treatment by helping define which tumors and which dose or timing strategies have the greatest potential from the treatment perspective. We will incorporate the dynamic details of these regressions into the clinically implementable models for angiogenic inhibitors currently being developed in our laboratory. Information about the dynamics of tumor vessel regression is also necessary for formation rational treatment protocols when combing angiogenic inhibitors with other therapies e.g. radiation or chemotherapy.
| Abdollahi, Amir; Hahnfeldt, Philip; Maercker, Christian et al. (2004) Endostatin's antiangiogenic signaling network. Mol Cell 13:649-63 |
| Hahnfeldt, Philip; Folkman, Judah; Hlatky, Lynn (2003) Minimizing long-term tumor burden: the logic for metronomic chemotherapeutic dosing and its antiangiogenic basis. J Theor Biol 220:545-54 |
