Epidermal growth factor receptor/angiogenesis dual targeting: preclinical experience.
OBJECTIVE
This review aims to critically examine the preclinical background regarding the combination of drugs targeting the epidermal growth factor receptor and anti-angiogenic compounds.


RESULTS
There are studies exploring the anti-tumor efficacy of dual inhibitors, such as the compound ZD6474, which combines in the same molecule an anti-tyrosine kinase activity against the epidermal growth factor receptor and the vascular endothelial growth factor receptor. In addition, several studies have investigated the anti-tumor effects of combinations of an anti-epidermal growth factor receptor agent and a vascular endothelial growth factor receptor inhibitor. In general, in these studies, supra-additive anti-tumor efficacy was apparent when combining anti-epidermal growth factor receptor and anti-angiogenic treatments. Beneficial effects were also observed when combining this dual targeted therapy with either conventional chemotherapy or irradiation.


CONCLUSIONS
Early clinical trials combining the anti-epidermal growth factor receptor drug erlotinib (Tarceva) and the anti-angiogenic agent bevacizumab (Avastin) show acceptable toxicity and promising anti-tumor activity (lung cancer), which need to be confirmed in randomized trials.
Bozec
Alexandre
A
Centre Antoine-Lacassagne, Nice, France.
Fischel
Jean-Louis
JL
Milano
Gerard
G
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D009389:Neovascularization, Pathologic; D010880:Piperidines / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010880:Piperidines; D011799:Quinazolines; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C452423:vandetanib