Drug News Perspect. 2007 Jun;20(5):307-13.
Antiangiogenic drugs currently used for colorectal cancer: what other pathways can we target to prolong responses?
Abbadessa G, Vogiatzi P, Rimassa L, Claudio PP.
Institute for Cancer Research and Molecular Medicine, College of
Science and Technology, Temple University, Philadelphia, Pennsylvania,
Angiogenesis plays a key role in
facilitating tumor growth and metastasis of colorectal cancer.
Considerable progress has been made in identifying molecular components
to develop angiogenesis-based treatments. Vascular endothelial growth
factor (VEGF) pathways are specific and critical regulators of
angiogenesis. However, other pathways are indirectly involved in
angiogenesis promotion and recent studies have confirmed it. This
review discusses known mechanisms involved in the action of
angiogenesis- related targeted drugs such as cetuximab (Erbitux) and
bevacizumab (Avastin), in patients affected by colorectal cancer. It
also elucidates the role of oxygen levels in cancer cell damage as well
as known alternative pathways used by tumoral cells to escape
hypoxic-related death. Hypoxia may in fact select resistant sub-clones
and boost tumor progression and growth, while the main subsequent
damages may be conferred by eventual re-oxygenation. Therefore, in the
light of the consolidated data available from the use of antiangiogenic
drugs, we discuss about a paradox that is forming: in the war against
tumoral angiogenesis it will be necessary to fight also the hypoxic
condition caused by the antiangiogenic drugs. (c) 2007 Prous Science.
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