Also, the shedding of large numbers of tumor cells from the primary tumor may not begin until after the tumor has a network of blood vessels. Inhibit normal endothelial cells directly. Block factors that stimulate angiogenesis. Block action of integrin, a molecule on the endothelial cell surface. Also, since anti-angiogenic drugs may not necessarily kill tumors, but rather hold them in check indefinitely, the endpoint of early clinical trials may be different than for standard therapies.
Drug resistance is a major problem with chemotherapy agents.
Most cancer cells are genetically unstable, more prone to mutations, and therefore likely to produce drug resistant cells. Since anti-angiogenic drugs target normal endothelial cells, which are genetically stable, drug resistance may not develop. So far, resistance has not been a major problem in long-term animal studies or in preliminary clinical trials. Finally, anti-angiogenesis therapy may prove useful in combination with therapy directly aimed at tumor cells. Because each therapy is aimed at a different cellular target, the hope is that the combination will prove more effective.