Targeting angiogenesis in lung cancer - Pitfalls in drug development.

In non-small-cell lung cancer, anti-angiogenic strategies like bevacizumab have developed into standard treatment options. New anti-angiogenic drugs like tyrosine kinase inhibitors generated optimistic results in phase II trials, but failed to translate into positive results in phase III trials. In this overview some critical aspects of the biology of tumor angiogenesis and potential pitfalls of anti-angiogenic drug development are discussed. These include the design of clinical trials, dosage of investigational drugs or the choice of combinational drugs, the lack of validated biomarkers and the complexity of the patho-biology of tumor angiogenesis. Future trials should also direct attention to the role of cigarette smoke and the stage of the disease, which is investigated.