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Antiangiogenic factors in melanoma

Bafaloukos, D.

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doi: 10.1097/01.cmr.0000382743.23097.66
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Metastatic Melanoma (MM) carries a dismal prognosis, as it is largely resistant to conventional cytotoxic chemotherapy, biochemotherapy and immunotherapy. There is, therefore, a pressing need to identify new effective treatments to improve outcomes from MM. There is currently a wealth of novel targeted therapies being tested in oncology and MM is an attractive model for investigation. One of the key biological processes that appears to be relevant to establishment and progression of most forms of cancer is ANGIOGENESIS. Innovative approaches in oncology drug development include anti-angiogenic strategies, in the form of monoclonal antibodies and small-molecule kinase inhibitors. These angiogenic management strategies may be divided into therapies targeting: proangiogenic ligands (bevacizumab, VEGF-Trap: aflibercept); kinases associated with cell surface receptors and growth factors pathways (sorafenib, axitinib, valatinib, erlotinib, imatinib); MMPs and intergrins (batimastat, marimastat, etaracizomab-abegrin) and potentially m TOR inhibitors (everolimus).

Given the existence of multiple alternative pathways mechanisms, it is unlikely that targeting a single angiogenic axis in isolation will be sufficient to achieve complete tumor control in melanoma, as exemplified by the negative trials conducted to date. Future approaches to tackling angiogenesis in MM should take into account not only the new and emerging agents with different mechanisms of action against angiogenic pathways. In this way, therapeutic synergism can potentially be achieved and drug resistance arising from monotherapy may be delayed.

© 2010 Lippincott Williams & Wilkins, Inc.