TY - JOUR
T1 - ErbB-targeted therapeutic approaches in human cancer
AU - Arteaga, Carlos L.
N1 - Funding Information:
Supported by NIH grant R01 CA80195 and Vanderbilt-Ingram Cancer Center Support Grant CA68485.
PY - 2003/3/10
Y1 - 2003/3/10
N2 - The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.
AB - The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.
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U2 - 10.1016/S0014-4827(02)00104-0
DO - 10.1016/S0014-4827(02)00104-0
M3 - Review article
C2 - 12648471
AN - SCOPUS:0037429652
SN - 0014-4827
VL - 284
SP - 122
EP - 130
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -