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)

The fact that a single blood vessel can support the life of thousands of tumor cells has been known for a long time. However, therapeutic strategies that aim to impair vascular development in tumors are only slowly emerging in the clinics. Nevertheless, the accumulation of data from many successful preclinical studies of the effects of a variety of drugs that target tumor vasculature provides clues that should help rationalize future treatment modalities for human tumors. Indeed, the 'old' view of an immature and non-functional vascular network within tumors has evolved and, in this article, we will show that the concept of tumor heterogeneity should be extended to the vascular compartment. In addition, we will review recent data documenting that both mature and immature vessels coexist within tumors and, importantly, that their relative density responds to a dynamic process that evolves with time and treatments.
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PMID:Targeting the tumor vascular compartment to improve conventional cancer therapy. 1538 Sep 38

Epsins, endocytic adaptor proteins required for internalization of ubiquitylated receptors, are generally upregulated in human cancers. It has been characterized that mice deficient of epsins in the endothelium inhibit tumor growth by dysregulating vascular endothelial growth factor receptor-2 (VEGFR2) signaling and non-productive tumor angiogenesis. Binding of the epsin ubiquitin (Ub)-interacting motif (UIM) with ubiquitylated VEGFR2 is a critical mechanism for epsin-dependent VEGFR2 endocytosis and degradation, indicative of epsin UIM as a potential therapeutic target. A Computer Assisted Drug Design approach was utilized to create the UIM mimetic peptides for the functional competition of epsin binding sites in ubiquitylated VEGFR2 in vivo. Specifically targeting VEGFR2 in the tumor vasculature, the chemically synthesized chimeric UIM peptide, UPI, causes non-functional tumor angiogenesis, retards tumor growth, and increases survival rates in several tumor models. The authors showed that UPI binds ubiquitylated VEGFR2 to form a supercomplex in an Ub-dependent fashion. Collectively, the UPI targeting strategy offers a potentially novel treatment for cancer patients who are resistant to current anti-angiogenic therapies. In this review, the authors outline the main points of this research specifically as a potential application for glioma tumor therapy.
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PMID:Mimetic peptide of ubiquitin-interacting motif of epsin as a cancer therapeutic-perspective in brain tumor therapy through regulating VEGFR2 signaling. 2990 36