TY - JOUR
T1 - Epidermal growth factor receptor dependence in human tumors
T2 - More than just expression?
AU - Arteaga, Carlos L.
PY - 2002
Y1 - 2002
N2 - The epidermal growth factor receptor (EGFR) is a rational target for antitumor strategies. EGFR signaling causes increased proliferation, decreased apoptosis, and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or highly expressed in a variety of human tumors of epithelial origin. ZD1839 (Iressa™) is an orally active, selective EGFR tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. The lack of a consistent method of evaluating levels of EGFR has caused a disparity in reports of the EGFR as a prognostic factor; however, for some tumors, EGFR is a strong prognostic indicator associated with more aggressive disease and reduced survival. So far, no clear association between EGFR levels and response to EGFR-targeted agents has been found. Preclinical studies with ZD1839 have noted a relationship between the two in some cases, but not others. EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR, including receptor mutations, heterodimerization with other members of this receptor family such as HER2 (erbB2), increased expression of (autocrine/paracrine) ligands, and alterations in molecules that control receptor signaling output. Each of these components could be assessed to give an indication of the magnitude of EGFR signal amplification. Evaluation of signaling components downstream from EGFR should provide information on the activation of the EGFR pathway. Until EGFR-based assays predictive of a response to receptor-targeted therapies are available, there is no clear justification for stratifying patients by EGFR status or excluding patients with low EGFR levels from trials with ZD1839 or other EGFR inhibitors.
AB - The epidermal growth factor receptor (EGFR) is a rational target for antitumor strategies. EGFR signaling causes increased proliferation, decreased apoptosis, and enhanced tumor cell motility and neo-angiogenesis. The EGFR is expressed or highly expressed in a variety of human tumors of epithelial origin. ZD1839 (Iressa™) is an orally active, selective EGFR tyrosine kinase inhibitor, which blocks signal transduction pathways implicated in proliferation and survival of cancer cells. The lack of a consistent method of evaluating levels of EGFR has caused a disparity in reports of the EGFR as a prognostic factor; however, for some tumors, EGFR is a strong prognostic indicator associated with more aggressive disease and reduced survival. So far, no clear association between EGFR levels and response to EGFR-targeted agents has been found. Preclinical studies with ZD1839 have noted a relationship between the two in some cases, but not others. EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR, including receptor mutations, heterodimerization with other members of this receptor family such as HER2 (erbB2), increased expression of (autocrine/paracrine) ligands, and alterations in molecules that control receptor signaling output. Each of these components could be assessed to give an indication of the magnitude of EGFR signal amplification. Evaluation of signaling components downstream from EGFR should provide information on the activation of the EGFR pathway. Until EGFR-based assays predictive of a response to receptor-targeted therapies are available, there is no clear justification for stratifying patients by EGFR status or excluding patients with low EGFR levels from trials with ZD1839 or other EGFR inhibitors.
KW - Cancer therapy
KW - EGFR-TKI
KW - Predictive factor
KW - Prognostic factor
KW - ZD1839 (Iressa™)
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U2 - 10.1634/theoncologist.7-suppl_4-31
DO - 10.1634/theoncologist.7-suppl_4-31
M3 - Review article
C2 - 12202786
AN - SCOPUS:0036362221
SN - 1083-7159
VL - 7
SP - 31
EP - 39
JO - Oncologist
JF - Oncologist
IS - SUPPL. 4
ER -