Antiangiogenesis: New frontiers in therapeutic development

  title={Antiangiogenesis: New frontiers in therapeutic development},
  author={Kenneth R Lamontagne},
  • K. Lamontagne
  • Published 7 January 2006
  • Biology, Medicine
  • Angiogenesis
It is almost 35 years ago that Harvard’s surgeon, Judah Folkman, hypothesized that tumor growth is angiogenesis dependent. That insight has lead to the explosion of interest in targeting tumor angiogenesis. In February of 2004, Genentech’s Avastin (bevacizumab), a humanized monoclonal antibody that blocks vascular endothelial growth factor (VEGF), was the first angiogenesis inhibitor to receive Food and Drug Administration (FDA) approval for the treatment of advanced colorectal cancer… 

Serum concentration and immunostaining of vascular endothelial growth factor in dogs with multicentric lymphoma Concentração sérica e imunomarcação do fator de crescimento do endotélio vascular em cães com linfoma multicêntrico

The results showed that VEGF is expressed in high amounts in the lymph nodes of dogs with multicentric lymphoma and may be responsible for the growth, survival and migration of this cancer.

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and Ktrans, could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.

Neuroangiogenesis: a vascular basis for Alzheimer's disease and cognitive decline during aging.

  • C. Ambrose
  • Psychology, Medicine
    Journal of Alzheimer's disease : JAD
  • 2012
It is proposed that neuroangiogenesis is essential throughout adult life for maintaining the microcirculation of the cerebral cortex and elsewhere in the brain and that it commonly declines with old age.



Vascular remodeling and clinical resistance to antiangiogenic cancer therapy.

The VEGF receptor tyrosine kinase inhibitor, ZD6474, inhibits angiogenesis and affects microvascular architecture within an orthotopically implanted renal cell carcinoma

In this RENCA model, ZD6474 was a highly active inhibitor of tumor angiogenesis, primary tumor growth and tumor metastasis, and quantitative three-dimensional microvascular corrosion casting was performed to enable detailed assessment of the tumor vascular architecture.

Antagonism of sphingosine-1-phosphate receptors by FTY720 inhibits angiogenesis and tumor vascularization.

It is shown here that FTY720 has antiangiogenic activity, potently abrogating VEGF- and S1P-induced angiogenesis in vivo in growth factor implant and corneal models and may provide a novel therapeutic approach for pathologic conditions with dysregulatedAngiogenesis.

Modeling metastasis in vivo.

The following review will summarize the strengths and weaknesses of available in vivo models of metastasis including transplantable syngeneic mouse and human-mouse xenografts, genetically engineered mice and naturally occurring cancers of companion animals (pet dogs and cats).

Increased Expression of Urinary Matrix Metalloproteinases Parallels the Extent and Activity of Vascular Anomalies

Urinary high molecular weight MMPs and bFGF were significantly increased in patients with vascular tumors and vascular malformations, compared with control subjects, suggesting that progression of a vascular malformation might be suppressed by angiogenic inhibitors.

Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Antiangiogenic Agent SU5416

Dose de-escalation of SU5416 does not result in decreased blood flow in tumors or a decrease in microvessel density, which corresponds to the lack of clinical activity seen with this agent.

Contribution of bone marrow–derived endothelial cells to human tumor vasculature

Substantial differences between human tumors and many mouse models with respect to angiogenesis are illustrated and have important implications for the translation of experimental antiangiogenic therapies to the clinic.

Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition.

Novel pyrazole compounds are shown to inhibit TGF-beta-induced Smad2 phosphorylation in vivo in NMuMg mammary epithelial cells with potency equivalent to the inhibitory activity in the in vitro kinase assay and provide a foundation for future development of potent and selective TbetaRI kinase inhibitors to treat human disease.

Prostate secretory protein of 94 amino acids (PSP-94) and its peptide (PCK3145) as potential therapeutic modalities for prostate cancer

Interestingly, equimolar concentrations of PCK3145 were shown to be more effective in delaying the development of experimental skeletal metastases as compared to PSP-94, and warrant the continued clinical development of these agents as therapeutic agents for patients with hormone-refractory prostate cancer.

Quantification of tumor tissue populations by multispectral analysis

KM clustering of the apparent diffusion coefficient, T2, and proton density was employed to estimate the volumes of viable tumor tissue, necrosis, and neighboring subcutaneous adipose tissue in a human colorectal tumor xenograft mouse model and shows promise as a means of detecting an early therapeutic response in vivo.