Growing tumor vessels: More than one way to skin a cat – Implications for angiogenesis targeted cancer therapies

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

“…Furthermore, the endothelial cells of tumor blood vessels can display features –fenestration patterns, pericyte and inflammatory‐cell association, proliferation and apoptosis rates, and gene expression profiles – that vary not only among different tumor types or individual tumors, but also in a local–regional manner within a given tumor. Such heterogeneity may be influenced by the site in which a tumor arises (i.e., the specific organ or tissue microenvironment), the tumor growth stage, the biophysical properties of the surrounding stroma (e.g., interstitial pressure, collagen cross‐linking and extra‐cellular matrix tension), and many other ill‐defined spatiotemporal differences such as angiogenic gene expression by tumor and stromal cells (Carmeliet and Jain, 2011a; Chung and Ferrara, 2011; Hanahan and Weinberg, 2011; Kerbel, 2008; Leite de Oliveira et al., 2011; McDonald and Choyke, 2003; Nagy et al., 2010; Potente et al., 2011; Weis and Cheresh, 2011). As a consequence of these many variables affecting vascular phenotypes, experimental tumors growing subcutaneously in mice may differ significantly from spontaneous tumors in terms of vascular density, functionality, phenotype, and gene expression.…”

“…Different human cancers are variably sensitive to antiangiogenic drugs (e.g., inhibitors of endothelial TK receptors or antibodies that block vascular growth factors); furthermore, tumors of a generally refractory type may sporadically show dramatic responses to antiangiogenic drugs (Carmeliet and Jain, 2011b; Chung et al., 2010; Goel et al., 2011; Leite de Oliveira et al., 2011). It can be argued that tumor type or subtype‐specific aspects of the biology of associated endothelial cells (e.g., gene expression programs) may have a role in determining such different responses.…”

“…Studies in GEMMs of cancer have begun elucidating the molecular bases of such variation. It has emerged, for example, that certain tumor types are less dependent on VEGF (and hence resistant to VEGF blockade) than others, as they can use noncanonical (e.g., non‐sprouting) modalities of vascular growth or alterative proangiogenic pathways for sprouting angiogenesis (Abdullah and Perez‐Soler, 2011; Bergers and Hanahan, 2008; Leite de Oliveira et al., 2011). For instance, some tumors can grow along pre‐existing blood vessels without evoking an angiogenic response (and indeed are refractory to VEGF blockade); this process is referred to as vascular co‐option (Carmeliet and Jain, 2011a) and is specially observed in well‐vascularized tissues such as the brain (Holash et al., 1999).…”

Modulation of Tumor Angiogenesis by a Host Anti-Tumor Response in Colorectal Cancer

“…Tumor cells attempt to overcome this issue by the expression of more pro-angiogenic factors such as VEGF resulting in amplified formation of abnormal vessels. However, tumor hypoxia cannot be rescued by the formation of abnormal vessels (Leite de Oliveira et al, 2011).…”

Long isoform of VEGF stimulates cell migration of breast cancer by filopodia formation via NRP1/ARHGAP17/Cdc42 regulatory network

“…Several mechanisms of this acquired resistance have been proposed, such as angiogenesis by alternative pro‐angiogenic pathways,10, 11, 12, 13 and recruitment of vascular progenitors14 and modulators 15, 16. In addition, hypoxia induced by anti‐angiogenic therapy promotes selection of aggressive cancer cells17 and expansion of cancer stem cell pool 18.…”