Inhibitors of growth factor receptors, signaling pathways and angiogenesis as therapeutic molecular agents

ArticleinCancer and metastasis reviews 25(2):243-52 · July 2006with8 Reads
DOI: 10.1007/s10555-006-8504-6 · Source: PubMed
    • "A second series of studies demonstrated that VEGF is a negative regulator of cell invasion in the case of glioblastoma multiforme (GBM), rapidly growing and highly aggressive grade IV astrocytomas (brain tumors) [24]. GBM are characterized by zones of necrosis and hypoxia and, as a result, typically express high levels of HIF-1 and downstream angiogenic factors such as VEGF, angiopoietin-2 and SDF-1α252627. They disrupt the blood-brain barrier and are characterized by extensive edema and an influx of inflammatory cells. "
    [Show abstract] [Hide abstract] ABSTRACT: Tumor blood vessels are heterogeneous, of at least six distinct types, are induced primarily by vascular endothelial growth factor-A (VEGF-A), and provide a potentially useful therapeutic target. Breast cancer is characterized by changes in the microenvironment that result in altered tensional homeostasis. Also, breast cancers arise as the result of epigenetic as well as genetic changes. Tumor blood vessel pericytes result, in part, from bone marrow precursor cells, and VEGF is a negative regulator of glioblastoma tumor cell invasion.
    Full-text · Article · May 2011
    • "In a rat model of hind limb ischaemia, combined delivery of Ang-1 and VEGF genes stimulated collateral vessel development to the greatest extent [160,161]. Thus far, therapy directed at VEGF has reached the clinic, but not therapy directed at Ang/Tie [162]. Targeting homeostasis and repair/inflammation in critically ill patients is an attractive option and has already led to the development of new drugs [45,158,163] . "
    [Show abstract] [Hide abstract] ABSTRACT: Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting multiple mechanisms at the same time, have appeared to be beneficial. We clearly need to understand better the mechanisms that underlie MODS. The endothelium certainly plays an active role in MODS. It functions at the intersection of several systems, including inflammation, coagulation, haemodynamics, fluid and electrolyte balance, and cell migration. An important regulator of these systems is the angiopoietin/Tie2 signalling system. In this review we describe this signalling system, giving special attention to what is known about it in critically ill patients and its potential as a target for therapy.
    Full-text · Article · Apr 2009
    • "In the light of our data, pericyte removal could also increase the risk for rapid metastasis. Combination therapy has been tested in several mouse tumour models including breast and prostate cancer, colon carcinoma[67] and bone metastasis (reviewed in [68]). In all cases, targeting PDGFRβ signalling proved to reduce tumour growth and metastasis and in limited human studies appears to improve prognosis. "
    [Show abstract] [Hide abstract] ABSTRACT: Tumour cells use two major routes to spread during metastasis, e.g. lymph vessels and blood vessels within or surrounding the primary tumour. The growth rate of the primary tumour often correlates with the quantity of new blood vessels that form within the tumour. However, qualitative abnormalities of the tumour vasculature profoundly affect the perfusion of the primary tumour and the escape of tumour cells into the circulation. In this paper, we review recent evidence for a novel role of the supporting mural cells in limiting blood-borne metastasis.
    Full-text · Article · Mar 2008
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