Antipericyte Drugs

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Science  23 May 2003:
Vol. 300, Issue 5623, pp. 1203
DOI: 10.1126/science.300.5623.1203b

Tumors require a blood supply for growth, and many new cancer therapies are designed to cut off that blood supply by disrupting the tumor vasculature. The majority of these drugs target the endothelial cells in the tumor vasculature, either by inhibiting their growth or by promoting their apoptosis. Recent work suggests that another constituent of tumor blood vessels—the pericytes (contractile cells that stabilize vessel walls)—may merit equal attention as a cellular target for cancer drugs.

Studying angiogenesis inhibitors in a mouse tumor model, Bergers et al. found that the therapeutic efficacy of an endothelial cell-targeted drug (a vascular endothelial growth factor receptor inhibitor) was greatly enhanced when it was combined with Gleevec, a drug that inhibits a protein expressed in pericytes: platelet-derived growth factor receptor. In independent work, Reinmuth et al. concluded that the anti-tumor efficacy of an αVβ3 integrin antagonist, another endothelial cell-targeted drug, was due in part to its impairment of pericyte function in the tumor vessels. Thus, combination cancer therapies targeting multiple components of the tumor vasculature may offer the greatest hope for clinical success.—PAK

J. Clin. Invest. 111, 1287 (2003); Cancer Res. 63, 2079 (2003).

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