TipcellPROANTIANGIOGENESISInadequateReturntoabnormalPROANTIPROANTIPROANTIPROANTIPericyteEndothelialcell(EC)BasementmembraneTumorcellsco-optpre-existingvesselsTumorcellslinetumorvesselsCancerstem-likecellsdifferentiatetoECsEndothelialprogenitorcell(EPC)differentiatestoECBONEMARROWVESSELCO-OPTIONVASCULARMIMICRYVASCULOGENESISINTUSSUSCEPTIONSPROUTINGANGIOGENESISTUMORSTEMCELLTOECDIFFERENTIATIONNORMALIZEDVESSELSNORMALIZATIONWINDOWCLOSEDABNORMALTUMORVESSELSNORMALVASCULATUREHowdotumorsrecruitbloodvessels?Howdoesanti-angiogenictherapywork?Seeonlineversionforlegendandreferences.SnapShot:TumorAngiogenesisRakeshK.Jain1andPeterCarmeliet21MassachusettsGeneralHospitalandHarvardMedicalSchool,Boston,MA02114,USA2VesaliusResearchCenter,VIBandK.U.Leuven,B-3000Leuven,Belgium1408Cell149,June8,2012©2012ElsevierInc.DOI10.1016/j.cell.2012.05.025Anti-angiopoietin/Tie2pathwayagents(inclinicaltrials)AMG386Ovarian,breast,gastric,hepatocellularcarcinoma,renalcellcarci-noma,endometrial,colorectalcarcinoma,glioblastomaCVX-060RenalcellcarcinomaCVX-241Ovarian,primaryperitonealMEDI-3617AdvancedsolidtumorsREGN910AdvancedsolidtumorsAMG-780AdvancedsolidtumorsCEP-1198AdvancedsolidtumorsARRY-614MyelodysplasticsyndromesMGCD265Advancedmalignancies,non-smallcelllungcarcinomaRegorafenibGastrointestinal,renalcellcarcinomaAnti-VEGfdrugs(2012)BevacizumabMetastaticcolorectalcancer,metastaticnonsquamousnon-smallcelllungcancer,metastaticbreastcancer,recurrentglioblastoma,metastaticrenalcellcarcinomaSunitinibMetastaticrenalcellcarcinoma,gastrointestinalstromaltumors,pancreaticneuroendocrinetumorsSorafenibMetastaticrenalcellcarcinoma,unresectablehepatocellularcarcinomaPazopanibMetastaticrenalcellcarcinoma,advancedsarcomaVandetanibAdvancedmedullarythyroidcancerAxitinibAdvancedrenalcellcarcinomaRegoranfenibMetastaticcolorectalcancer(approvalpending)AfliberceptMetastaticcolorectalcancer(approvalpending)1408.e1Cell149,June8,2012©2012ElsevierInc.DOI10.1016/j.cell.2012.05.025SnapShot:TumorAngiogenesisRakeshK.Jain1andP...
