Antiangiogenic drugs and current strategies for the treatment of lung cancer.

Significant advances in the treatment of lung cancers, especially advanced-stage non-small cell lung cancer, have been marginal despite decades of intensive basic research and clinical trial testing. Among the newest class of promising drugs being tested is the angiogenesis inhibitor. The recent success of a randomized phase III trial testing an antivascular endothelial growth factor (VEGF) antibody with chemotherapy for the treatment of metastatic colon cancer has raised hopes that antiangiogenic drugs will have similar benefits for the treatment of lung cancer. Ironically, the sheer number and diversity of such drugs makes selecting the most promising candidates difficult. More detailed and definitive information on the specific factors that induce angiogenesis in types of lung cancer, such as the relative importance of VEGF or other proangiogenic growth factors in non-small cell lung cancer, small cell lung cancer, and mesothelioma angiogenesis, is therefore clearly needed. The nonangiogenic phenotype of some non-small cell lung cancers may render this subset particularly difficult to treat with angiogenesis inhibitors; such tumors, however, may be promising candidates for acute-acting vascular-targeting agents. As with other types of cancer, success with angiogenesis inhibitors will no doubt depend on a number of factors including screening patients' tumors for presence or absence of a particular drug target (eg, bioactive VEGF receptor-2 bound VEGF) when targeting VEGF, selecting the optimal biologic/therapeutic doses of antiangiogenic drugs, monitoring antiangiogenic drug activity in tumors, and determining optimal combinations to use with chemotherapy regimens.