RESUMEN
The use of vascular endothelial growth factor (VEGF)-targeted agents for treating cancer has increased dramatically over recent decades. These drugs provide considerable benefits in terms of progression-free (PFS) or overall (OS) survival for cancer patients. Of particular importance to clinicians treating cancer patients by using VEGF-targeted agents is VEGF-inhibition-induced hypertension, proteinuria, thrombosis and hemorrhage. Aflibercept is a new, successful example of targeting VEGF for therapy of solid tumors. Though results from phase I and II clinical trials demonstrated aflibercept is well tolerated, it inevitably has severe adverse effects unique to this class of agents. In this review, we discuss the adverse effects associated with aflibercept (VEGF Trap), focusing on vascularassociated hypertension, proteinuria, hemorrhage, and thrombosis, and further discuss the mechanisms, significance, and potential management of these adverse effects.
Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Neoplasias/irrigación sanguínea , Neoplasias/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Proteínas Recombinantes de Fusión/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Ensayos Clínicos como Asunto , Hemorragia/inducido químicamente , Humanos , Hipertensión/inducido químicamente , Proteinuria/inducido químicamente , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión/uso terapéutico , Trombosis/inducido químicamente , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Mouse cancer models have consistently been used to qualify new anticancer drugs in the development of human clinical trials. Rodent tumour models currently being used and which include transgenic tumour models, and those generated by planting human tumour cell lines subcutaneously in immunodeficient mice, do not sufficiently represent clinical cancer characteristics, especially with regard to metastasis and drug sensitivity. The increasingly used patient-derived human tumour tissue (PDTT) xenografts models implanted subcutaneously or in subrenal capsule in immunodeficient mice, such as athymic nude mice or severe combined immunedeficient (SCID) mice, may provide a more accurate reflection of human tumour biological characteristics than tumour cell lines. The ability to passage patients' fresh tumour tissues into large numbers of immunodeficient mice provides possibilities for better preclinical testing of new therapies for the treatment and better outcome for cancer. In this review, we outline the methods of establishing xenograft models, discuss the biological stability of PDTT xenograft models and demonstrate their roles in developing new anticancer drugs and testing therapeutic regimens in cancer patients.