Resistance in the anti-angiogenic era: nay-saying or a word of caution?

The hope that anti-angiogenic therapy might be the panacea for cancer has not yet been realized. There are many possible reasons for this, including endothelial and tumor cell heterogeneity, the presence of survival factors within the tumor micro-environment, the problem of defining the best dose and schedule for anti-angiogenic therapies, and angiogenesis-independent regrowth of tumors. Once these problems are understood, we can begin to evaluate approaches to thwarting them. These could include combining anti-angiogenic therapies with chemotherapy, with other anti-angiogenic agents or with other biological therapies. Another approach would be to employ a particular agent or combination of agents that target processes crucial to the survival of a particular cancer.