Molecular determinants of angiogenesis in cancer metastasis
Fidler, I.J.; Kumar, R.; Bielenberg, D.R.; Ellis, L.M.
Cancer Journal from Scientific American 4(Suppl 1): S58-S66
1998
ISSN/ISBN: 1081-4442 PMID: 9619272 Document Number: 3491
Continuous growth of neoplasms and the production of metastases depend on the formation of adequate blood supply. The extent of angiogenesis is determined by the balance between positive and negative regulating molecules. The cross-talk between tumor and stromal cells occurs mainly via a complex network of extracellular signals, including cytokines and growth factors, their antagonists/inhibitors, and soluble receptors, all of which are released by and act on cells within the tumor microenvironment. Antiangiogenesis therapy does not lead to the death of all tumor cells but, rather, restricts their growth beyond a spheroid 1 mm in diameter. This form of therapy could be directed against the tumor endothelium, basement membrane, angiogenic peptides, degradative enzymes (required for morphogenesis of blood vessels), extracellular matrix proteins (also necessary for blood vessel morphogenesis), and angiogenic factors or angiogenic factor receptors. To be effective, it is likely that any antiangiogenesis treatment will have to be administered for a prolonged time. A case in point is the report of regression of fatal hemangiomas in infants treated daily with IFN-a for more than 9 months. The success of this antiangiogenic therapy was due in part to the ability of the clinical scientists to monitor the level of serum bFGE, which declined several weeks before any measurable regression, and to administer daily IFN-a injections. The mechanisms that regulate angiogenesis in tumors of different histologic origins, among tumors of the same histologic origin growing in different metastatic sites, and even within a single tumor are likely to be diverse. To maximize the efficacy of antiangiogenic therapy, it may be necessary to determine the angiogenic profile of individual tumors and to tailor the treatment plan accordingly.
Document emailed within 1 workday
