Besides bevacizumab, several other VEGF inhibitors are being clinically pursued.Followup of such phase III data is ongoing to determine whether an overall survival benefit occurs.An earlier randomized phase II study had shown that bevacizumab as a single agent also results in an increase in time to progression in renal cell carcinoma patients, providing further evidence that this tumour type may be particularly responsive to antiVEGF treatment.AG, which has a similar spectrum of kinase inhibition to SU, has also shown promise in metastatic renal cell carcinoma in a phase II monotherapy study. Twentyfour patients experienced partial responses to the treatment.Stable disease was observed in an additional patients. These interesting efficacy data will need to be followed by an appropriately designed and powered phase III trial.An additional VEGF RTK inhibitor in latestage clinical trials is PTK. This molecule is in phase III trials in colorectal cancer patients, in combination with FOLFOX chemotherapy.Recently, interim findings of this trial have been presented. However, a central review failed to document any significant difference.Subgroup analysis suggested that patients with high lactic dehydrogenase have the best response to PTK in terms of progressionfree survival.A chimaeric, soluble VEGF receptor is also undergoing clinical development as an anticancer agent and preliminary results of a phase I study have been recently presented J.Currently, several antiVEGF strategies are being explored in AMD clinical trials.Pegaptanib has been approved by the FDA for the treatment of AMD, after phase III studies showing that intraocular administrations of the drug reduced visual loss relative to the placebo.Very recently, data of a controlled phase III study with ranibizumab indicated that the treatment is efficacious and maintains or improves vision in patients with wet AMD. There is emerging evidence that VEGFA may be replaced by other angiogenic pathways as the disease progresses.Other possible mechanisms for acquired resistance to antiangiogenic drugs, include selection and overgrowth of tumourcell variants that are hypoxic resistant and thus less dependent on angiogenesis and tumourvessel remodelling resulting in a shift to mature, stabilized vessels that are less responsive to antiangiogenic drugs.The recruitment of bonemarrowderived angiogenic cells may also provide a potential mechanism of escape to some antiangiogenic strategies.A current focus of research is the role of myeloid cells of the monocytemacrophage lineage in mediating multiple pathways leading to tumour progression and angiogenesis. The hypoxic tumour microenvironment may lead to upregulation of chemokines and other factors and hepatocyte growth factor from tumourinfiltrating macrophages, which may facilitate angiogenesis, Dutasteride invasion and immune evasion of tumours.Furthermore, recent studies suggest that in some cases endothelial cells associated with tumours are not a genetically stable, nontransformed, compartment and instead may provide a further mechanism of resistance to antiangiogenic therapies.Many angiogenic factors are active in a variety of animal Cozymase models of coronary or limb ischaemia. On the basis of these preclinical data, several angiogenic factors have been tested in patients with myocardial or limb ischaemia.Although promising results were initially reported in small openlabel trials, none of the placebocontrolled trials so far conducted with recombinant proteins or gene therapy has yielded convincingly positive results.