Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1658953 (tumor vasculature)
 2,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aflibercept, also known as vascular endothelial growth factor (VEGF)-Trap, is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting not only all forms of VEGF-A, but also VEGF-B and placental growth factor. It inhibits VEGF-induced angiogenesis in preclinical models. In tumor models, aflibercept is associated with the reduction of tumor vasculature and size, and the inhibition of ascites formation. Clinical studies are investigating the use of aflibercept alone and in combination with other antineoplastic therapies for the treatment of various cancers. Phase I and II studies have provided proof of principle, and support the continuing clinical investigation of aflibercept. Results from the phase III study, VITAL, of aflibercept in the second-line setting in patients with advanced non-small cell lung cancer [NCT00532155] demonstrated efficacy in progression-free survival and overall objective response rate, but overall survival was not significantly improved. A full report awaits publication. The Phase III VANILLA trial in metastatic pancreatic cancer [NCT00574275] showed no improvement in overall survival. Most recently, the phase III VELOUR study [NCT00561470] of aflibercept plus FOLFIRI compared with placebo plus FOLFIRI in patients with metastatic colorectal cancer following failure of an oxaliplatin regimen showed significant improvements in overall survival, progression-free survival, and response rate and the complete results have been submitted to a peer-reviewed journal. This review summarizes preclinical and clinical data for aflibercept and discusses future directions and clinical trials for this agent.
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PMID:A preclinical and clinical review of aflibercept for the management of cancer. 2226 50

Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels. FDA has recently approved Aflibercept or VEGF-Trap in August 2012 for the treatment of colorectal cancer. It is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting VEGF-A, VEGF-B and placental growth factor. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remodelling or normalization of surviving vasculature and inhibition of new tumor vessel growth. In this review, pre-clinical and clinical data have been summarized for aflibercept alone and in combination with chemotherapy to explore its efficacy and benefits in ovarian cancer, breast cancer, non-small cell lung cancer, pancreatic cancer, glioblastoma, adenocarcinoma and renal cell cancer xenograft models.
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PMID:Aflibercept: a novel VEGF targeted agent to explore the future perspectives of anti-angiogenic therapy for the treatment of multiple tumors. 2331 99

Angiogenesis is the process through which new blood vessels are formed from pre-existing vessels and is essential for the growth of all solid tumors. Vascular endothelial growth factor (VEGF) is a regulator of angiogenesis, which is crucial for tumor growth and metastasis. Its inhibition with antiangiogenic drugs is thought to improve delivery of chemotherapy through vascular normalization and disruption of tumor vasculature. Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR)1 and VEGFR2 extracellular domains that binds to VEGF-A, VEGF-B, placental growth factor (PlGF) 1 and 2. Aflibercept has demonstrated preclinical efficacy in different tumor types and exerts its antiangiogenic effects through regression of tumor vasculature, remolding of vasculature, and inhibition of new tumor vessel growth. This review examines the effects of aflibercept on tumor vasculature and on different types of solid tumors, and explores the preclinical and clinical benefits of inclusion aflibercept into anticancer treatment strategies.
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PMID:Aflibercept a new target therapy in cancer treatment: a review. 2622 65