Inhibiting angiogenesis is a promising strategy for treatment of cancer and several other disorders, including age-related macular degeneration. Major progress towards a treatment has been achieved over the past few years, and the first antiangiogenic agents have been recently approved for use in several countries. Therapeutic angiogenesis (promoting new vessel growth to treat ischaemic disorders) is an exciting frontier of cardiovascular medicine, but further understanding of the mechanisms of vascular morphogenesis is needed first.
describe more molecular details of Dll-notch receptor signaling and the domain structure of the receptor. VEGFR-2 denotes vascular endothelial growth factor receptor 2. Kerbel
SUMMARY
Herein we report that the VEGFR/PDGFR kinase inhibitor sunitinib/SU11248 can accelerate metastatic tumor growth and decrease overall survival in mice receiving short-term therapy in various metastasis assays, including after intravenous injection of tumor cells or after removal of primary orthotopically grown tumors. Acceleration of metastasis was also observed in mice receiving sunitinib prior to intravenous implantation of tumor cells, suggesting possible “metastatic conditioning” in multiple organs. Similar findings with additional VEGF receptor tyrosine kinase inhibitors implicate a class-specific effect for such agents. Importantly, these observations of metastatic acceleration were in contrast to the demonstrable antitumor benefits obtained when the same human breast cancer cells, as well as mouse or human melanoma cells, were grown orthotopically as primary tumors and subjected to identical sunitinib treatments.
Angiogenesis inhibitors are a new class of drugs, for which the general rules involving conventional chemotherapy might not apply. The successful translation of angiogenesis inhibitors to clinical application depends partly on the transfer of expertise from scientists who are familiar with the biology of angiogenesis to clinicians. What are the most common questions that clinicians ask as they begin to test angiogenesis inhibitors in cancer clinical trials?
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