Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors

摘要: Functions of receptor tyrosine kinases implicated in angiogenesis were pharmacologically impaired a mouse model pancreatic islet cancer. An inhibitor targeting VEGFRs endothelial cells (SU5416) is effective against early-stage angiogenic lesions, but not large, well-vascularized tumors. In contrast, kinase incorporating selectivity for PDGFRs (SU6668) shown to block further growth end-stage tumors, eliciting detachment pericytes and disruption tumor vascularity. Importantly, expressed only perivascular this type, suggesting that PDGFR+ tumors present complimentary target efficacious antiangiogenic therapy. Therapeutic regimes combining the two inhibitors (SU5416 SU6668) more all stages carcinogenesis than either single agent. Combination VEGFR with another distinctive PDGFR activity (Gleevec) was also able regress late-stage Thus, combinatorial shows promise treating multiple tumorigenesis, most notably often-intractable solid tumor. This article published online advance print edition. The date publication available from JCI website, http://www.jci.org. J. Clin. Invest. 111:1287‐1295 (2003). doi:10.1172/JCI200317929.