Precipitating an Invasion

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Science  27 Mar 2009:
Vol. 323, Issue 5922, pp. 1647
DOI: 10.1126/science.323.5922.1647b

Anti-angiogenic drugs for cancer have commanded tremendous interest, especially over the past decade as they entered long-awaited clinical trials. This class of compounds inhibits the growth of tumors by cutting off their blood supply, usually by disabling cellular signaling pathways that are essential for blood vessel growth, such as the vascular endothelial growth factor (VEGF) pathway. Despite an abundance of promising preclinical data, most cancer patients have shown only a transient improvement in response to VEGF-targeting drugs, which is then followed by a progression to metastatic disease.

Two groups show that VEGF-targeting drugs have unanticipated—and undesirable—effects on tumor behavior that might explain their limited clinical efficacy. Working with four distinct mouse models, Pàez-Ribes et al. and Ebos et al. find that although the drugs initially inhibit primary tumor growth, they also appear to stimulate tumor cells to develop a more invasive and metastatic phenotype. This might occur because the drugs cause hypoxia (oxygen deficiency), which in turn selects for more malignant cells, or because the drugs increase the leakiness of blood vessels, thereby facilitating the entry of tumor cells into the circulation. — PAK

Cancer Cell 15, 220; 232 (2009).

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