Antiangiogenic drugs currently used for colorectal cancer: what other pathways can we target to prolong responses?
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.
Abbadessa
Giovanni
G
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, USA.
Vogiatzi
Paraskevi
P
Rimassa
Lorenza
L
Claudio
Pier Paolo
PP
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000503:physiopathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D066246:ErbB Receptors; D000068818:Cetuximab