Although anti-angiogenesis agents targeting vascular endothelial growth factor (VEGF) pathways are already in clinical use and can effectively treat some cancers, there is a continued need for development of new angiogenesis inhibitors to circumvent resistance or reduce toxicity. To highlight the important topics in this evolving field Nature Reviews Cancer presents a Focus on Targeting Angiogenesis.
The topics covered in this specially-commissioned series of Reviews include the mechanisms by which VEGF antagonists kill tumour cells, novel mechanisms of resistance to anti-VEGF drugs and advances in identifying additional targets for anti-angiogenic therapy, such as members of the integrin and semaphorin families. These articles together with some recent Research Highlights and the accompanying library of the most relevant recent publications from Nature Research, describe our current understanding of this field. Furthermore, this Focus highlights the importance of gaining a greater understanding of the contribution of the tumour-associated vasculature to tumour growth and anticancer therapy.
Foreword: Limiting supply
doi:10.1038/nrc2461
Nature Reviews Cancer 8, 577 (2008)
Research Highlights
Angiogenesis: TGFβ makes a new friend
Safia Ali Danovi
doi:10.1038/nrc2448
Nature Reviews Cancer 8, 572 (2008)
Angiogenesis: Turning it down a Notch
Safia Ali Danovi
doi:10.1038/nrc2450
Nature Reviews Cancer 8, 572-573 (2008)
Angiogenesis: Survival of the infected
Katharine H. Wrighton
doi:10.1038/nrc2452
Nature Reviews Cancer 8, 569 (2008)
Angiogenesis: A less bitter pill
Patrick Goymer
doi:10.1038/nrc2463
Nature Reviews Cancer 8, 567 (2008)
Angiogenesis: Mini mediator of metastasis suppression
Nicola McCarthy
doi:10.1038/nrc2453
Nature Reviews Cancer 8, 570-571 (2008)
Targeting thyroid angiogenesis
doi:10.1038/nrc2456
Nature Reviews Cancer 8, 573 (2008)
Reviews
VEGF-targeted therapy: mechanisms of anti-tumour activity
Lee M. Ellis & Daniel J. Hicklin
doi:10.1038/nrc2403
Nature Reviews Cancer 8, 579-591 (2008)
The therapeutic benefit associated with VEGF-targeted therapy is complex, and probably involves multiple mechanisms, several of which are covered in this Review. Understanding these mechanisms more fully should lead to future advances in the use of these agents in the clinic.
Modes of resistance to anti-angiogenic therapy
Gabriele Bergers & Douglas Hanahan
doi:10.1038/nrc2442
Nature Reviews Cancer 8, 592-603 (2008)
In both preclinical and clinical settings, the benefits of angiogenesis inhibitors targeting the vascular endothelial growth factor signalling pathways are at best transitory and followed by restoration of tumour growth and progression. Emerging data support a proposition that two modes of unconventional resistance underlie such results.
Integrins in angiogenesis and lymphangiogenesis
Christie J. Avraamides, Barbara Garmy-Susini & Judith A. Varner
doi:10.1038/nrc2353
Nature Reviews Cancer 8, 604-617 (2008)
Angiogenesis and lymphangiogenesis are regulated by integrins, which are cell surface receptors whose ligands are extracellular matrix proteins and immunoglobulin superfamily molecules. Here, the evidence implicating integrins as regulators of angiogenesis and lymphangiogenesis and the current state of therapeutic strategies to target them are discussed.
The role of myeloid cells in the promotion of tumour angiogenesis
Craig Murdoch, Munitta Muthana, Seth B. Coffelt & Claire E. Lewis
doi:10.1038/nrc2444
Nature Reviews Cancer 8, 618-631 (2008)
Bone marrow-derived myeloid cells, such as macrophages and mast cells, have an important role in regulating the formation and maintenance of blood vessels in tumours. How do these cells contribute to this process?
The semaphorins: versatile regulators of tumour progression and tumour angiogenesis
Gera Neufeld & Ofra Kessler
doi:10.1038/nrc2404
Nature Reviews Cancer 8, 632-645 (2008)
The semaphorins and their receptors, the neuropilins and the plexins, originally characterized as proteins involved in the guidance of axons, can either promote or inhibit tumour progression. This Review documents their effects on tumour angiogenesis, as well as on metastasis and cell survival.
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