Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Células de los Islotes Pancreáticos/irrigación sanguínea , Carcinoma de Células de los Islotes Pancreáticos/tratamiento farmacológico , Cronoterapia , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Pancreáticas/irrigación sanguínea , Neoplasias Pancreáticas/tratamiento farmacológico , Fenilalanina/análogos & derivados , Animales , Indoles/antagonistas & inhibidores , Inhibidores de la Metaloproteinasa de la Matriz , Ratones , Fenilalanina/antagonistas & inhibidores , Inhibidores de Proteasas/administración & dosificación , Pirroles/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Tiofenos/antagonistas & inhibidoresRESUMEN
Solid tumors depend on angiogenesis for their growth. In a transgenic mouse model of pancreatic islet cell carcinogenesis (RIP1-Tag2), an angiogenic switch occurs in premalignant lesions, and angiogenesis persists during progression to expansive solid tumors and invasive carcinomas. RIP1-Tag2 mice were treated so as to compare the effects of four angiogenesis inhibitors at three distinct stages of disease progression. AGM-1470, angiostatin, BB-94, and endostatin each produced distinct efficacy profiles in trials aimed at preventing the angiogenic switch in premalignant lesions, intervening in the rapid expansion of small tumors, or inducing the regression of large end-stage cancers. Thus, anti-angiogenic drugs may prove most efficacious when they are targeted to specific stages of cancer.