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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.
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.
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.
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 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.
M. Judah Folkman is regarded by many as the father of research into the therapeutic targeting of angiogenesis. For cancer research, what were his most notable achievements?
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. Articles in this Focus issue describe some of the emerging targets for new anti-angiogenic therapies in cancer and also discuss our evolving knowledge of VEGF inhibitors based on results from the clinic.
