Abstract
Epidermal growth factor receptor (EGFR)/HER1 is expressed at high levels in at least 20% of breast cancers. This high expression correlates with a poor prognosis in patients with breast cancer. Experimental and clinical findings suggest that aberrant activation of tyrosine receptor kinases, such as HER1 pathway, play a causal role in the development of antiestrogen resistance in breast cancer. Recent preclinical and clinical evidence shows that inhibition of growth factor signaling pathways suppresses the growth of malignant cells without serious toxicities. To test the hypothesis that inhibition of the HER1 signaling pathway enhances the antitumor effect of endocrine therapy, a promising signal transduction inhibitor (STI) of HER1 tyrosine kinase, gefitinib, and an estrogen receptor (ER) antagonist, fulvestrant, were administered to human breast cancer cells. Our experimental results have revealed that gefitinib additively enhances the antitumor effect of fulvestrant in estrogen receptor (ER)-positive breast cancer cells under estrogen-supplemented conditions. An additive increase in the protein expression level of a cyclin-dependent kinase inhibitor, p21 may play a key role of this additive cytostatic effect. The rationale and future perspectives of the combined use of STIs with endocrine therapy in breast cancer are discussed.
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Abbreviations
- EGFR:
-
Epidermal growth factor receptor
- HER:
-
Human epidermal growth factor receptor
- PI3K:
-
Phosphatidylinositol-3-OH-kinase
- ER:
-
Estrogen receptor
- STI:
-
Signal transduction inhibitor
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Kurebayashi, J., Okubo, S., Yamamoto, Y. et al. Inhibition of HER1 signaling pathway enhances antitumor effect of endocrine therapy in breast cancer. Breast Cancer 11, 38–41 (2004). https://doi.org/10.1007/BF02968000
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DOI: https://doi.org/10.1007/BF02968000