Overview of angiogenesis: Biologic implications for antiangiogenic therapy

Ellis, Lee M.; Liu, Wenbiao; Ahmad, Syed A.; Fan, Fan; Jung, Young Do; Shaheen, Raymond M.; Reinmuth, Niels

doi:10.1053/sonc.2001.28560

Cited by 25 publications

(35 citation statements)

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“…In fact, current investigations towards the development of agents that target tumour vascularization aim to exploit this 'Achille's heel' of the tumour blood vessel network. Rapid efforts in recent years have now resulted in the identification of a variety of potential targets and a large number of investigational drugs and agents capable of targeting tumour blood vessels have been actively pursued (Arap, 1998;Ellis, 2001;Kerbel, 2000;Pastorino, 2007;Ruoslahti, 2002;Siemann and Horsman, 2009). The application of vascular targeting strategies as adjuvant to standard therapeutic modalities may offer unique opportunities to develop even more effective cancer therapies.…”

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confidence: 99%

“…Secondly, the fact that a large number of cancer cells depend upon a small number of endothelial cells for their growth and survival, therapies against the tumour endothelium might also amplify their therapeutic effects (Jain, 2001). Finally, the therapeutic targets are partially independent of the type of solid tumour; killing of proliferating endothelial cells in the tumour microenvironment can be effective against a large amount of cells in a variety of malignancies.Vascular targeting therapies fall into two general categories based on whether they interfere with new blood vessel development (angiogenesis inhibitors, AIs) or damage the established tumour vasculature (vascular disrupting agents, VDAs) (Bloemendal, 1999;Ellis, 2001;Siemann, 2004b;Thorpe, 2004). AIs seek to inhibit the tumour-initiated angiogenic process by interrupting essential aspects of angiogenesis, most notably signalling between the tumour and endothelial and stromal cells, and endothelial cell functions in order to prevent new blood vessel formation (Siemann and Horsman, 2009).…”

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confidence: 99%

“…Vascular targeting therapies fall into two general categories based on whether they interfere with new blood vessel development (angiogenesis inhibitors, AIs) or damage the established tumour vasculature (vascular disrupting agents, VDAs) (Bloemendal, 1999;Ellis, 2001;Siemann, 2004b;Thorpe, 2004). AIs seek to inhibit the tumour-initiated angiogenic process by interrupting essential aspects of angiogenesis, most notably signalling between the tumour and endothelial and stromal cells, and endothelial cell functions in order to prevent new blood vessel formation (Siemann and Horsman, 2009).…”

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confidence: 99%

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The use of the orthotopic model to validate antivascular therapies for cancer

Loi¹,

Paolo²,

Becherini³

et al. 2011

Int. J. Dev. Biol.

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The orthotopic model reproduces aspects of the tumour microenvironment and emulates a number of important biological features of cancer progression, angiogenesis, metastasis and resistance. Due to its parallels with human cancer, the model can be used to evaluate therapeutic responses to various therapies. This review outlines the importance of using the orthotopic implantation of tumour cells in mice models for evaluating the effectiveness of antivascular therapies. KEY WORDS: orthotopic model, vascular disrupting agent, antivascular therapy, cancer Tumour vasculature and antivascular therapiesA functioning and continuously expanding vascular network is essential for tumour development, growth, survival and metastasis (Hanahan and Folkman, 1996). Given its pivotal role in these processes, tumour vasculature is a highly attractive target in anticancer therapy. Compared with the vasculature in normal tissue, the tumour vasculature is strikingly disorganized and tortuous (Eberhard, 2000;Konerding, 2001;McDonald and Choyke, 2003), its wall is poorly developed, often with discontinuous endothelial-cell lining, has relatively poor investiture with vascular smooth muscle cells, poor connections between pericytes and endothelial cells (Dvorak, 1988;Eberhard, 2000;Hashizume, 2000;Kobayashi, 1993) and an irregular, structurally abnormal basement membrane (Baluk, 2003;Paku and Paweletz, 1991). Endothelial cells themselves are often irregularly shaped, forming an uneven luminal layer, with loose interconnections and focal intercellular openings (Hashizume, 2000). These features contribute to a high intrinsic vascular permeability of macromolecules into the vasculature (Dvorak, 1991;Jain, 1987) and the consequent development of high interstitial fluid pressure (Boucher, 1990), which is augmented by inadequate lymphatic drainage. Tumour vascular networks are chaotic, featuring complex branching patterns and lack of hierarchy (Gillies, 1999;Konerding, 1999;Less, 1991). Vessel diameters are irregular and lengths between branching points are often very long. The result is a high geometrical resistance to blood flow, that such as small decreases in perfusion pressure, which have little Int. J. Dev. Biol. 55: [547][548][549][550][551][552][553][554][555] doi: 10.1387/ijdb.103230ml www.intjdevbiol.com *Address correspondence to: Mirco Ponzoni or Fabio Pastorino. Experimental Therapies Unit, Laboratory of Oncology, G. Gaslini Children's Hospital, 16148-Genoa, Italy. Tel: +39-010-5636342. Fax: +39-010-3779820. e-mail: mircoponzoni@ospedale-gaslini.ge.it or fabiopastorino@ospedale-gaslini.ge.it # These Authors share the last co-authorship. effect in normal tissues, can be catastrophic in tumours (Sevick and Jain, 1989). Capillary blood contains abnormally high levels of deoxygenated blood (Mueller-Klieser, 1981), which, combined with heterogeneous blood flow and large intercapillary distances, contributes to micro-regional hypoxia in tumours (Vaupel and Hockel, 2000). The tumour is also starved of nutrient, under acidic cond...

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The use of the orthotopic model to validate antivascular therapies for cancer

Loi¹,

Paolo²,

Becherini³

et al. 2011

Int. J. Dev. Biol.

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“…Given its pivotal role in tumor survival, progression and spread, factors known to contribute signifi cantly to treatment failures, agents capable of targeting tumor blood vessels have been actively pursued (Folkman and Shing, 1992;Arap, Pasqualini and Ruoslahti, 1998;Ruoslahti, 2002;Ellis et al, 2001;Kerbel, 2000). Indeed it is now well recognized that strategies directed against the tumor blood vessel network may offer not only unique therapeutic opportunities in their own right but also novel means of enhancing the effi cacies of conventional anticancer treatments.…”

Section: Vascular-targeting Therapiesmentioning

confidence: 99%

“…Indeed it is now well recognized that strategies directed against the tumor blood vessel network may offer not only unique therapeutic opportunities in their own right but also novel means of enhancing the effi cacies of conventional anticancer treatments. Vascular-targeting therapies that endeavor to take advantage of unique features of the microvessel networks in tumors fall into two general categories based on whether they interfere with new blood vessel development or damage the established tumor vasculature (Thorpe, 2004;Ellis et al, 2001;Bloemendal, Logtenberg and Voest, 1999;Siemann, Chaplin and Horsman, 2004). The fi rst aims to inhibit the tumor-initiated angiogenic process itself.…”

Section: Vascular-targeting Therapiesmentioning

confidence: 99%

Tumor Vasculature: a Target for Anticancer Therapies

Siemann

2006

Vascular‐Targeted Therapies in Oncology

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Role of angiogenesis in chronic lymphocytic leukemia

Letilović

Vrhovać

Verstovšek

et al. 2006

Cancer

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Angiogenesis is a physiologic process of new blood vessels formation mediated by various cytokines called angiogenic and angiostatic factors. Although its potential pathophysiologic role in solid tumors has been extensively studied for more than 3 decades, enhancement of angiogenesis in chronic lymphocytic leukemia (CLL) and other malignant hematological disorders has been recognized more recently.An increased level of angiogenesis has been documented by various experimental methods both in bone marrow and lymph nodes of patients with CLL. Although the role of angiogenesis in the pathophysiology of this disease remains to be fully elucidated, experimental data suggest that several angiogenic factors play a role in the disease progression. Biologic markers of angiogenesis were also shown to be of prognostic relevance in CLL. The current findings provide the rationale for investigating antiangiogenic agents in CLL. In the current review angiogenesis in CLL is discussed and its potential diagnostic and therapeutic applications. Cancer 2006;107:925-34.

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Overview of angiogenesis: Biologic implications for antiangiogenic therapy

Cited by 25 publications

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The use of the orthotopic model to validate antivascular therapies for cancer

The use of the orthotopic model to validate antivascular therapies for cancer

Tumor Vasculature: a Target for Anticancer Therapies

Role of angiogenesis in chronic lymphocytic leukemia

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